Links to Exploration step
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension</title><author><name sortKey="Surendran, Praveen" sort="Surendran, Praveen" uniqKey="Surendran P" first="Praveen" last="Surendran">Praveen Surendran</name><affiliation><nlm:aff id="A1">Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Drenos, Fotios" sort="Drenos, Fotios" uniqKey="Drenos F" first="Fotios" last="Drenos">Fotios Drenos</name><affiliation><nlm:aff id="A2">Medical Research Council Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A3">Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, Rayne Building University College London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Young, Robin" sort="Young, Robin" uniqKey="Young R" first="Robin" last="Young">Robin Young</name><affiliation><nlm:aff id="A1">Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Warren, Helen" sort="Warren, Helen" uniqKey="Warren H" first="Helen" last="Warren">Helen Warren</name><affiliation><nlm:aff id="A4">Clinical Pharmacology, William Harvey Research Institute, Queen Mary University of London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A5">National Institute for Health Research Barts Cardiovascular Biomedical Research Unit, Queen Mary University of London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Cook, James P" sort="Cook, James P" uniqKey="Cook J" first="James P" last="Cook">James P. Cook</name><affiliation><nlm:aff id="A6">Department of Health Sciences, University of Leicester, Leicester, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A7">Department of Biostatistics, University of Liverpool, Liverpool, UK</nlm:aff></affiliation></author><author><name sortKey="Manning, Alisa K" sort="Manning, Alisa K" uniqKey="Manning A" first="Alisa K" last="Manning">Alisa K. Manning</name><affiliation><nlm:aff id="A8">Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A9">Program in Medical and Population Genetics, Broad Institute, 7 Cambridge Center, Cambridge, Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A10">Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Grarup, Niels" sort="Grarup, Niels" uniqKey="Grarup N" first="Niels" last="Grarup">Niels Grarup</name><affiliation><nlm:aff id="A11">The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark</nlm:aff></affiliation></author><author><name sortKey="Sim, Xueling" sort="Sim, Xueling" uniqKey="Sim X" first="Xueling" last="Sim">Xueling Sim</name><affiliation><nlm:aff id="A12">Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A13">Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A14">Saw Swee Hock School of Public Health, National University of Singapore, National University Health System, Singapore</nlm:aff></affiliation></author><author><name sortKey="Barnes, Daniel R" sort="Barnes, Daniel R" uniqKey="Barnes D" first="Daniel R" last="Barnes">Daniel R. Barnes</name><affiliation><nlm:aff id="A1">Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Witkowska, Kate" sort="Witkowska, Kate" uniqKey="Witkowska K" first="Kate" last="Witkowska">Kate Witkowska</name><affiliation><nlm:aff id="A4">Clinical Pharmacology, William Harvey Research Institute, Queen Mary University of London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A5">National Institute for Health Research Barts Cardiovascular Biomedical Research Unit, Queen Mary University of London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Staley, James R" sort="Staley, James R" uniqKey="Staley J" first="James R" last="Staley">James R. Staley</name><affiliation><nlm:aff id="A1">Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Tragante, Vinicius" sort="Tragante, Vinicius" uniqKey="Tragante V" first="Vinicius" last="Tragante">Vinicius Tragante</name><affiliation><nlm:aff id="A15">Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Tukiainen, Taru" sort="Tukiainen, Taru" uniqKey="Tukiainen T" first="Taru" last="Tukiainen">Taru Tukiainen</name><affiliation><nlm:aff id="A8">Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A9">Program in Medical and Population Genetics, Broad Institute, 7 Cambridge Center, Cambridge, Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A16">Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Yaghootkar, Hanieh" sort="Yaghootkar, Hanieh" uniqKey="Yaghootkar H" first="Hanieh" last="Yaghootkar">Hanieh Yaghootkar</name><affiliation><nlm:aff id="A17">Genetics of Complex Traits, Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK</nlm:aff></affiliation></author><author><name sortKey="Masca, Nicholas" sort="Masca, Nicholas" uniqKey="Masca N" first="Nicholas" last="Masca">Nicholas Masca</name><affiliation><nlm:aff id="A18">Department of Cardiovascular Sciences, University of Leicester, Leicester, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A19">National Institute for Health Research Leicester Biomedical Research Unit in Cardiovascular Disease, Leicester, UK</nlm:aff></affiliation></author><author><name sortKey="Freitag, Daniel F" sort="Freitag, Daniel F" uniqKey="Freitag D" first="Daniel F" last="Freitag">Daniel F. Freitag</name><affiliation><nlm:aff id="A1">Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Ferreira, Teresa" sort="Ferreira, Teresa" uniqKey="Ferreira T" first="Teresa" last="Ferreira">Teresa Ferreira</name><affiliation><nlm:aff id="A20">Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK</nlm:aff></affiliation></author><author><name sortKey="Giannakopoulou, Olga" sort="Giannakopoulou, Olga" uniqKey="Giannakopoulou O" first="Olga" last="Giannakopoulou">Olga Giannakopoulou</name><affiliation><nlm:aff id="A21">Heart Centre, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Tinker, Andrew" sort="Tinker, Andrew" uniqKey="Tinker A" first="Andrew" last="Tinker">Andrew Tinker</name><affiliation><nlm:aff id="A21">Heart Centre, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A5">National Institute for Health Research Barts Cardiovascular Biomedical Research Unit, Queen Mary University of London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Harakalova, Magdalena" sort="Harakalova, Magdalena" uniqKey="Harakalova M" first="Magdalena" last="Harakalova">Magdalena Harakalova</name><affiliation><nlm:aff id="A15">Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Mihailov, Evelin" sort="Mihailov, Evelin" uniqKey="Mihailov E" first="Evelin" last="Mihailov">Evelin Mihailov</name><affiliation><nlm:aff id="A22">Estonian Genome Center, University of Tartu, Tartu, Estonia</nlm:aff></affiliation></author><author><name sortKey="Liu, Chunyu" sort="Liu, Chunyu" uniqKey="Liu C" first="Chunyu" last="Liu">Chunyu Liu</name><affiliation><nlm:aff id="A23">National Heart, Lung, and Blood Institute’s and Boston University’s Framingham Heart Study, Framingham, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Kraja, Aldi T" sort="Kraja, Aldi T" uniqKey="Kraja A" first="Aldi T" last="Kraja">Aldi T. Kraja</name><affiliation><nlm:aff id="A24">Division of Statistical Genomics, Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, Missouri, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A25">Department of Genetics, Washington University School of Medicine, St. Louis, Missouri, USA</nlm:aff></affiliation></author><author><name sortKey="Fallgaard Nielsen, Sune" sort="Fallgaard Nielsen, Sune" uniqKey="Fallgaard Nielsen S" first="Sune" last="Fallgaard Nielsen">Sune Fallgaard Nielsen</name><affiliation><nlm:aff id="A26">Department of Clinical Biochemistry Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark</nlm:aff></affiliation></author><author><name sortKey="Rasheed, Asif" sort="Rasheed, Asif" uniqKey="Rasheed A" first="Asif" last="Rasheed">Asif Rasheed</name><affiliation><nlm:aff id="A27">Centre for Non-Communicable Diseases, Karachi, Pakistan</nlm:aff></affiliation></author><author><name sortKey="Samuel, Maria" sort="Samuel, Maria" uniqKey="Samuel M" first="Maria" last="Samuel">Maria Samuel</name><affiliation><nlm:aff id="A27">Centre for Non-Communicable Diseases, Karachi, Pakistan</nlm:aff></affiliation></author><author><name sortKey="Zhao, Wei" sort="Zhao, Wei" uniqKey="Zhao W" first="Wei" last="Zhao">Wei Zhao</name><affiliation><nlm:aff id="A28">Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA</nlm:aff></affiliation></author><author><name sortKey="Bonnycastle, Lori L" sort="Bonnycastle, Lori L" uniqKey="Bonnycastle L" first="Lori L" last="Bonnycastle">Lori L. Bonnycastle</name><affiliation><nlm:aff id="A29">Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA</nlm:aff></affiliation></author><author><name sortKey="Jackson, Anne U" sort="Jackson, Anne U" uniqKey="Jackson A" first="Anne U" last="Jackson">Anne U. Jackson</name><affiliation><nlm:aff id="A13">Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A12">Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA</nlm:aff></affiliation></author><author><name sortKey="Narisu, Narisu" sort="Narisu, Narisu" uniqKey="Narisu N" first="Narisu" last="Narisu">Narisu Narisu</name><affiliation><nlm:aff id="A29">Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA</nlm:aff></affiliation></author><author><name sortKey="Swift, Amy J" sort="Swift, Amy J" uniqKey="Swift A" first="Amy J" last="Swift">Amy J. Swift</name><affiliation><nlm:aff id="A29">Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA</nlm:aff></affiliation></author><author><name sortKey="Southam, Lorraine" sort="Southam, Lorraine" uniqKey="Southam L" first="Lorraine" last="Southam">Lorraine Southam</name><affiliation><nlm:aff id="A30">Wellcome Trust Sanger Institute, Genome Campus, Hinxton, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A20">Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK</nlm:aff></affiliation></author><author><name sortKey="Marten, Jonathan" sort="Marten, Jonathan" uniqKey="Marten J" first="Jonathan" last="Marten">Jonathan Marten</name><affiliation><nlm:aff id="A31">Medical Research Council Human Genetics Unit, Medical Research Council Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Huyghe, Jeroen R" sort="Huyghe, Jeroen R" uniqKey="Huyghe J" first="Jeroen R" last="Huyghe">Jeroen R. Huyghe</name><affiliation><nlm:aff id="A13">Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A12">Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA</nlm:aff></affiliation></author><author><name sortKey="Stan Kova, Alena" sort="Stan Kova, Alena" uniqKey="Stan Kova A" first="Alena" last="Stan Ková">Alena Stan Ková</name><affiliation><nlm:aff id="A32">Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland</nlm:aff></affiliation></author><author><name sortKey="Fava, Cristiano" sort="Fava, Cristiano" uniqKey="Fava C" first="Cristiano" last="Fava">Cristiano Fava</name><affiliation><nlm:aff id="A33">University of Lund, Department of Clinical Sciences, Malmö, Sweden</nlm:aff></affiliation><affiliation><nlm:aff id="A34">University of Verona, Department of Medicine, Verona, Italy</nlm:aff></affiliation></author><author><name sortKey="Ohlsson, Therese" sort="Ohlsson, Therese" uniqKey="Ohlsson T" first="Therese" last="Ohlsson">Therese Ohlsson</name><affiliation><nlm:aff id="A33">University of Lund, Department of Clinical Sciences, Malmö, Sweden</nlm:aff></affiliation></author><author><name sortKey="Matchan, Angela" sort="Matchan, Angela" uniqKey="Matchan A" first="Angela" last="Matchan">Angela Matchan</name><affiliation><nlm:aff id="A30">Wellcome Trust Sanger Institute, Genome Campus, Hinxton, UK</nlm:aff></affiliation></author><author><name sortKey="Stirrups, Kathleen E" sort="Stirrups, Kathleen E" uniqKey="Stirrups K" first="Kathleen E" last="Stirrups">Kathleen E. Stirrups</name><affiliation><nlm:aff id="A21">Heart Centre, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A35">Department of Haematology, University of Cambridge, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Bork Jensen, Jette" sort="Bork Jensen, Jette" uniqKey="Bork Jensen J" first="Jette" last="Bork-Jensen">Jette Bork-Jensen</name><affiliation><nlm:aff id="A11">The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark</nlm:aff></affiliation></author><author><name sortKey="Gjesing, Anette P" sort="Gjesing, Anette P" uniqKey="Gjesing A" first="Anette P" last="Gjesing">Anette P. Gjesing</name><affiliation><nlm:aff id="A11">The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark</nlm:aff></affiliation></author><author><name sortKey="Kontto, Jukka" sort="Kontto, Jukka" uniqKey="Kontto J" first="Jukka" last="Kontto">Jukka Kontto</name><affiliation><nlm:aff id="A36">Department of Health, National Institute for Health and Welfare, Helsinki, Finland</nlm:aff></affiliation></author><author><name sortKey="Perola, Markus" sort="Perola, Markus" uniqKey="Perola M" first="Markus" last="Perola">Markus Perola</name><affiliation><nlm:aff id="A36">Department of Health, National Institute for Health and Welfare, Helsinki, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A37">Institute of Molecular Medicine FIMM, University of Helsinki, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A22">Estonian Genome Center, University of Tartu, Tartu, Estonia</nlm:aff></affiliation></author><author><name sortKey="Shaw Hawkins, Susan" sort="Shaw Hawkins, Susan" uniqKey="Shaw Hawkins S" first="Susan" last="Shaw-Hawkins">Susan Shaw-Hawkins</name><affiliation><nlm:aff id="A4">Clinical Pharmacology, William Harvey Research Institute, Queen Mary University of London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Havulinna, Aki S" sort="Havulinna, Aki S" uniqKey="Havulinna A" first="Aki S" last="Havulinna">Aki S. Havulinna</name><affiliation><nlm:aff id="A36">Department of Health, National Institute for Health and Welfare, Helsinki, Finland</nlm:aff></affiliation></author><author><name sortKey="Zhang, He" sort="Zhang, He" uniqKey="Zhang H" first="He" last="Zhang">He Zhang</name><affiliation><nlm:aff id="A38">Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan, USA</nlm:aff></affiliation></author><author><name sortKey="Donnelly, Louise A" sort="Donnelly, Louise A" uniqKey="Donnelly L" first="Louise A" last="Donnelly">Louise A. Donnelly</name><affiliation><nlm:aff id="A39">Medical Research Institute, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK</nlm:aff></affiliation></author><author><name sortKey="Groves, Christopher J" sort="Groves, Christopher J" uniqKey="Groves C" first="Christopher J" last="Groves">Christopher J. Groves</name><affiliation><nlm:aff id="A40">Oxford Centre for Diabetes, Endocrinology, and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK</nlm:aff></affiliation></author><author><name sortKey="Rayner, N William" sort="Rayner, N William" uniqKey="Rayner N" first="N William" last="Rayner">N William Rayner</name><affiliation><nlm:aff id="A40">Oxford Centre for Diabetes, Endocrinology, and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A20">Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A30">Wellcome Trust Sanger Institute, Genome Campus, Hinxton, UK</nlm:aff></affiliation></author><author><name sortKey="Neville, Matt J" sort="Neville, Matt J" uniqKey="Neville M" first="Matt J" last="Neville">Matt J. Neville</name><affiliation><nlm:aff id="A40">Oxford Centre for Diabetes, Endocrinology, and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A41">National Institute for Health Research Oxford Biomedical Research Centre, Oxford University Hospital Trusts, Oxford, UK</nlm:aff></affiliation></author><author><name sortKey="Robertson, Neil R" sort="Robertson, Neil R" uniqKey="Robertson N" first="Neil R" last="Robertson">Neil R. Robertson</name><affiliation><nlm:aff id="A20">Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A40">Oxford Centre for Diabetes, Endocrinology, and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK</nlm:aff></affiliation></author><author><name sortKey="Yiorkas, Andrianos M" sort="Yiorkas, Andrianos M" uniqKey="Yiorkas A" first="Andrianos M" last="Yiorkas">Andrianos M. Yiorkas</name><affiliation><nlm:aff id="A42">Section of Investigative Medicine, Imperial College London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A43">Department of Life Sciences, Brunel University London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Herzig, Karl Heinz" sort="Herzig, Karl Heinz" uniqKey="Herzig K" first="Karl-Heinz" last="Herzig">Karl-Heinz Herzig</name><affiliation><nlm:aff id="A44">Institute of Biomedicine, Biocenter Oulu, University of Oulu, Oulu, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A45">Department of Gastroenterology and Metabolism, Poznan University of Medical Sciences, Poznan, Poland</nlm:aff></affiliation></author><author><name sortKey="Kajantie, Eero" sort="Kajantie, Eero" uniqKey="Kajantie E" first="Eero" last="Kajantie">Eero Kajantie</name><affiliation><nlm:aff id="A36">Department of Health, National Institute for Health and Welfare, Helsinki, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A46">Hospital for Children and Adolescents, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A47">Department of Obstetrics and Gynaecology, Oulu University Hospital and University of Oulu, Oulu, Finland</nlm:aff></affiliation></author><author><name sortKey="Zhang, Weihua" sort="Zhang, Weihua" uniqKey="Zhang W" first="Weihua" last="Zhang">Weihua Zhang</name><affiliation><nlm:aff id="A48">Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A49">Department of Cardiology, Ealing Hospital, Middlesex, UK</nlm:aff></affiliation></author><author><name sortKey="Willems, Sara M" sort="Willems, Sara M" uniqKey="Willems S" first="Sara M" last="Willems">Sara M. Willems</name><affiliation><nlm:aff id="A50">Medical Research Council Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Lannfelt, Lars" sort="Lannfelt, Lars" uniqKey="Lannfelt L" first="Lars" last="Lannfelt">Lars Lannfelt</name><affiliation><nlm:aff id="A51">Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden</nlm:aff></affiliation></author><author><name sortKey="Malerba, Giovanni" sort="Malerba, Giovanni" uniqKey="Malerba G" first="Giovanni" last="Malerba">Giovanni Malerba</name><affiliation><nlm:aff id="A52">Section of Biology and Genetics, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy</nlm:aff></affiliation></author><author><name sortKey="Soranzo, Nicole" sort="Soranzo, Nicole" uniqKey="Soranzo N" first="Nicole" last="Soranzo">Nicole Soranzo</name><affiliation><nlm:aff id="A53">Human Genetics, Wellcome Trust Sanger Institute, Hinxton, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A35">Department of Haematology, University of Cambridge, Cambridge, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A54">The National Institute for Health Research Blood and Transplant Research Unit in Donor Health and Genomics, University of Cambridge, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Trabetti, Elisabetta" sort="Trabetti, Elisabetta" uniqKey="Trabetti E" first="Elisabetta" last="Trabetti">Elisabetta Trabetti</name><affiliation><nlm:aff id="A52">Section of Biology and Genetics, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy</nlm:aff></affiliation></author><author><name sortKey="Verweij, Niek" sort="Verweij, Niek" uniqKey="Verweij N" first="Niek" last="Verweij">Niek Verweij</name><affiliation><nlm:aff id="A55">University Medical Center Groningen, University of Groningen, Department of Cardiology, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A9">Program in Medical and Population Genetics, Broad Institute, 7 Cambridge Center, Cambridge, Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A56">Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Evangelou, Evangelos" sort="Evangelou, Evangelos" uniqKey="Evangelou E" first="Evangelos" last="Evangelou">Evangelos Evangelou</name><affiliation><nlm:aff id="A48">Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A57">Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece</nlm:aff></affiliation></author><author><name sortKey="Moayyeri, Alireza" sort="Moayyeri, Alireza" uniqKey="Moayyeri A" first="Alireza" last="Moayyeri">Alireza Moayyeri</name><affiliation><nlm:aff id="A48">Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A58">Farr Institute of Health Informatics Research, Institute of Health Informatics, University College London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Vergnaud, Anne Claire" sort="Vergnaud, Anne Claire" uniqKey="Vergnaud A" first="Anne-Claire" last="Vergnaud">Anne-Claire Vergnaud</name><affiliation><nlm:aff id="A48">Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Nelson, Christopher P" sort="Nelson, Christopher P" uniqKey="Nelson C" first="Christopher P" last="Nelson">Christopher P. Nelson</name><affiliation><nlm:aff id="A18">Department of Cardiovascular Sciences, University of Leicester, Leicester, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A19">National Institute for Health Research Leicester Biomedical Research Unit in Cardiovascular Disease, Leicester, UK</nlm:aff></affiliation></author><author><name sortKey="Poveda, Alaitz" sort="Poveda, Alaitz" uniqKey="Poveda A" first="Alaitz" last="Poveda">Alaitz Poveda</name><affiliation><nlm:aff id="A59">Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, Sweden</nlm:aff></affiliation><affiliation><nlm:aff id="A60">Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Bilbao, Spain</nlm:aff></affiliation></author><author><name sortKey="Varga, Tibor V" sort="Varga, Tibor V" uniqKey="Varga T" first="Tibor V" last="Varga">Tibor V. Varga</name><affiliation><nlm:aff id="A59">Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, Sweden</nlm:aff></affiliation></author><author><name sortKey="Caslake, Muriel" sort="Caslake, Muriel" uniqKey="Caslake M" first="Muriel" last="Caslake">Muriel Caslake</name><affiliation><nlm:aff id="A61">University of Glasgow, Glasgow, UK</nlm:aff></affiliation></author><author><name sortKey="De Craen, Anton Jm" sort="De Craen, Anton Jm" uniqKey="De Craen A" first="Anton Jm" last="De Craen">Anton Jm De Craen</name><affiliation><nlm:aff id="A62">Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A63">Mr. De Craen suddenly passed away January 2016</nlm:aff></affiliation></author><author><name sortKey="Trompet, Stella" sort="Trompet, Stella" uniqKey="Trompet S" first="Stella" last="Trompet">Stella Trompet</name><affiliation><nlm:aff id="A62">Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A64">Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Luan, Jian N" sort="Luan, Jian N" uniqKey="Luan J" first="Jian N" last="Luan">Jian N Luan</name><affiliation><nlm:aff id="A50">Medical Research Council Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Scott, Robert A" sort="Scott, Robert A" uniqKey="Scott R" first="Robert A" last="Scott">Robert A. Scott</name><affiliation><nlm:aff id="A50">Medical Research Council Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Harris, Sarah E" sort="Harris, Sarah E" uniqKey="Harris S" first="Sarah E" last="Harris">Sarah E. Harris</name><affiliation><nlm:aff id="A65">Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A66">Centre for Genomic and Experimental Medicine, Medical Research Council Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Liewald, David Cm" sort="Liewald, David Cm" uniqKey="Liewald D" first="David Cm" last="Liewald">David Cm Liewald</name><affiliation><nlm:aff id="A65">Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A67">Department of Psychology, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Marioni, Riccardo" sort="Marioni, Riccardo" uniqKey="Marioni R" first="Riccardo" last="Marioni">Riccardo Marioni</name><affiliation><nlm:aff id="A65">Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A66">Centre for Genomic and Experimental Medicine, Medical Research Council Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A68">Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia</nlm:aff></affiliation></author><author><name sortKey="Menni, Cristina" sort="Menni, Cristina" uniqKey="Menni C" first="Cristina" last="Menni">Cristina Menni</name><affiliation><nlm:aff id="A69">Department of Twin Research and Genetic Epidemiology, King’s College London, UK</nlm:aff></affiliation></author><author><name sortKey="Farmaki, Aliki Eleni" sort="Farmaki, Aliki Eleni" uniqKey="Farmaki A" first="Aliki-Eleni" last="Farmaki">Aliki-Eleni Farmaki</name><affiliation><nlm:aff id="A70">Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece</nlm:aff></affiliation></author><author><name sortKey="Hallmans, Goran" sort="Hallmans, Goran" uniqKey="Hallmans G" first="Göran" last="Hallmans">Göran Hallmans</name><affiliation><nlm:aff id="A71">Department of Biobank Research, Umeå University, Umeå, Sweden</nlm:aff></affiliation></author><author><name sortKey="Renstrom, Frida" sort="Renstrom, Frida" uniqKey="Renstrom F" first="Frida" last="Renström">Frida Renström</name><affiliation><nlm:aff id="A59">Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, Sweden</nlm:aff></affiliation><affiliation><nlm:aff id="A71">Department of Biobank Research, Umeå University, Umeå, Sweden</nlm:aff></affiliation></author><author><name sortKey="Huffman, Jennifer E" sort="Huffman, Jennifer E" uniqKey="Huffman J" first="Jennifer E" last="Huffman">Jennifer E. Huffman</name><affiliation><nlm:aff id="A31">Medical Research Council Human Genetics Unit, Medical Research Council Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A23">National Heart, Lung, and Blood Institute’s and Boston University’s Framingham Heart Study, Framingham, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Hassinen, Maija" sort="Hassinen, Maija" uniqKey="Hassinen M" first="Maija" last="Hassinen">Maija Hassinen</name><affiliation><nlm:aff id="A72">Kuopio Research Institute of Exercise Medicine, Kuopio, Finland</nlm:aff></affiliation></author><author><name sortKey="Burgess, Stephen" sort="Burgess, Stephen" uniqKey="Burgess S" first="Stephen" last="Burgess">Stephen Burgess</name><affiliation><nlm:aff id="A1">Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Vasan, Ramachandran S" sort="Vasan, Ramachandran S" uniqKey="Vasan R" first="Ramachandran S" last="Vasan">Ramachandran S. Vasan</name><affiliation><nlm:aff id="A23">National Heart, Lung, and Blood Institute’s and Boston University’s Framingham Heart Study, Framingham, Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A73">Section of Cardiology, Department of Medicine, Boston University Schools of Medicine and Public Health, Boston, Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A74">Sections of Preventive Medicine and Epidemiology, Department of Medicine, Boston University Schools of Medicine and Public Health, Boston, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Felix, Janine F" sort="Felix, Janine F" uniqKey="Felix J" first="Janine F" last="Felix">Janine F. Felix</name><affiliation><nlm:aff id="A75">Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Uria Nickelsen, Maria" sort="Uria Nickelsen, Maria" uniqKey="Uria Nickelsen M" first="Maria" last="Uria-Nickelsen">Maria Uria-Nickelsen</name><affiliation><nlm:aff id="A77">Development Management and Planning, Pfizer Worldwide Research and Development</nlm:aff></affiliation></author><author><name sortKey="Malarstig, Anders" sort="Malarstig, Anders" uniqKey="Malarstig A" first="Anders" last="Malarstig">Anders Malarstig</name><affiliation><nlm:aff id="A78">Pfizer Worldwide Research and Development, Stockholm, Sweden</nlm:aff></affiliation></author><author><name sortKey="Reily, Dermot F" sort="Reily, Dermot F" uniqKey="Reily D" first="Dermot F" last="Reily">Dermot F. Reily</name><affiliation><nlm:aff id="A79">Merck Research Laboratories, Genetics and Pharmacogenomics, Boston, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Hoek, Maarten" sort="Hoek, Maarten" uniqKey="Hoek M" first="Maarten" last="Hoek">Maarten Hoek</name><affiliation><nlm:aff id="A80">Merck Research Laboratories, Cardiometabolic Disease, Kenilworth, New Jersey, USA</nlm:aff></affiliation></author><author><name sortKey="Vogt, Thomas" sort="Vogt, Thomas" uniqKey="Vogt T" first="Thomas" last="Vogt">Thomas Vogt</name><affiliation><nlm:aff id="A80">Merck Research Laboratories, Cardiometabolic Disease, Kenilworth, New Jersey, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A81">CHDI Management/CHDI Foundation, Princeton, New Jersey, USA</nlm:aff></affiliation></author><author><name sortKey="Lin, Honghuang" sort="Lin, Honghuang" uniqKey="Lin H" first="Honghuang" last="Lin">Honghuang Lin</name><affiliation><nlm:aff id="A23">National Heart, Lung, and Blood Institute’s and Boston University’s Framingham Heart Study, Framingham, Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A82">Section of Computational Biomedicine, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Lieb, Wolfgang" sort="Lieb, Wolfgang" uniqKey="Lieb W" first="Wolfgang" last="Lieb">Wolfgang Lieb</name><affiliation><nlm:aff id="A83">Institute of Epidemiology and Biobank Popgen, Kiel University, Kiel, Germany</nlm:aff></affiliation></author><author><name sortKey="Traylor, Matthew" sort="Traylor, Matthew" uniqKey="Traylor M" first="Matthew" last="Traylor">Matthew Traylor</name><affiliation><nlm:aff id="A84">Neurology Unit, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Markus, Hugh F" sort="Markus, Hugh F" uniqKey="Markus H" first="Hugh F" last="Markus">Hugh F. Markus</name><affiliation><nlm:aff id="A84">Neurology Unit, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Highland, Heather M" sort="Highland, Heather M" uniqKey="Highland H" first="Heather M" last="Highland">Heather M. Highland</name><affiliation><nlm:aff id="A85">University of North Carolina at Chapel Hill, Department of Epidemiology, Chapel Hill, North Carolina, USA</nlm:aff></affiliation></author><author><name sortKey="Justice, Anne E" sort="Justice, Anne E" uniqKey="Justice A" first="Anne E" last="Justice">Anne E. Justice</name><affiliation><nlm:aff id="A85">University of North Carolina at Chapel Hill, Department of Epidemiology, Chapel Hill, North Carolina, USA</nlm:aff></affiliation></author><author><name sortKey="Marouli, Eirini" sort="Marouli, Eirini" uniqKey="Marouli E" first="Eirini" last="Marouli">Eirini Marouli</name><affiliation><nlm:aff id="A21">Heart Centre, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Lindstrom, Jaana" sort="Lindstrom, Jaana" uniqKey="Lindstrom J" first="Jaana" last="Lindström">Jaana Lindström</name><affiliation><nlm:aff id="A36">Department of Health, National Institute for Health and Welfare, Helsinki, Finland</nlm:aff></affiliation></author><author><name sortKey="Uusitupa, Matti" sort="Uusitupa, Matti" uniqKey="Uusitupa M" first="Matti" last="Uusitupa">Matti Uusitupa</name><affiliation><nlm:aff id="A86">Department of Public Health and Clinical Nutrition, University of Eastern Finland, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A87">Research Unit, Kuopio University Hospital, Kuopio, Finland</nlm:aff></affiliation></author><author><name sortKey="Komulainen, Pirjo" sort="Komulainen, Pirjo" uniqKey="Komulainen P" first="Pirjo" last="Komulainen">Pirjo Komulainen</name><affiliation><nlm:aff id="A72">Kuopio Research Institute of Exercise Medicine, Kuopio, Finland</nlm:aff></affiliation></author><author><name sortKey="Lakka, Timo A" sort="Lakka, Timo A" uniqKey="Lakka T" first="Timo A" last="Lakka">Timo A. Lakka</name><affiliation><nlm:aff id="A72">Kuopio Research Institute of Exercise Medicine, Kuopio, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A88">Institute of Biomedicine/Physiology, University of Eastern Finland, Kuopio Campus, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A89">Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland</nlm:aff></affiliation></author><author><name sortKey="Rauramaa, Rainer" sort="Rauramaa, Rainer" uniqKey="Rauramaa R" first="Rainer" last="Rauramaa">Rainer Rauramaa</name><affiliation><nlm:aff id="A72">Kuopio Research Institute of Exercise Medicine, Kuopio, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A89">Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland</nlm:aff></affiliation></author><author><name sortKey="Polasek, Ozren" sort="Polasek, Ozren" uniqKey="Polasek O" first="Ozren" last="Polasek">Ozren Polasek</name><affiliation><nlm:aff id="A90">Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A91">Faculty of Medicine, University of Split, Croatia</nlm:aff></affiliation></author><author><name sortKey="Rudan, Igor" sort="Rudan, Igor" uniqKey="Rudan I" first="Igor" last="Rudan">Igor Rudan</name><affiliation><nlm:aff id="A90">Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Rolandsson, Olov" sort="Rolandsson, Olov" uniqKey="Rolandsson O" first="Olov" last="Rolandsson">Olov Rolandsson</name><affiliation><nlm:aff id="A92">Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden</nlm:aff></affiliation></author><author><name sortKey="Franks, Paul W" sort="Franks, Paul W" uniqKey="Franks P" first="Paul W" last="Franks">Paul W. Franks</name><affiliation><nlm:aff id="A59">Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, Sweden</nlm:aff></affiliation><affiliation><nlm:aff id="A92">Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden</nlm:aff></affiliation><affiliation><nlm:aff id="A93">Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Dedoussis, George" sort="Dedoussis, George" uniqKey="Dedoussis G" first="George" last="Dedoussis">George Dedoussis</name><affiliation><nlm:aff id="A70">Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece</nlm:aff></affiliation></author><author><name sortKey="Spector, Timothy D" sort="Spector, Timothy D" uniqKey="Spector T" first="Timothy D" last="Spector">Timothy D. Spector</name><affiliation><nlm:aff id="A69">Department of Twin Research and Genetic Epidemiology, King’s College London, UK</nlm:aff></affiliation></author><author><name sortKey="Jousilahti, Pekka" sort="Jousilahti, Pekka" uniqKey="Jousilahti P" first="Pekka" last="Jousilahti">Pekka Jousilahti</name><affiliation><nlm:aff id="A36">Department of Health, National Institute for Health and Welfare, Helsinki, Finland</nlm:aff></affiliation></author><author><name sortKey="M Nnisto, Satu" sort="M Nnisto, Satu" uniqKey="M Nnisto S" first="Satu" last="M Nnistö">Satu M Nnistö</name><affiliation><nlm:aff id="A36">Department of Health, National Institute for Health and Welfare, Helsinki, Finland</nlm:aff></affiliation></author><author><name sortKey="Deary, Ian J" sort="Deary, Ian J" uniqKey="Deary I" first="Ian J" last="Deary">Ian J. Deary</name><affiliation><nlm:aff id="A65">Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A67">Department of Psychology, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Starr, John M" sort="Starr, John M" uniqKey="Starr J" first="John M" last="Starr">John M. Starr</name><affiliation><nlm:aff id="A65">Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A94">Alzheimer Scotland Research Centre, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Langenberg, Claudia" sort="Langenberg, Claudia" uniqKey="Langenberg C" first="Claudia" last="Langenberg">Claudia Langenberg</name><affiliation><nlm:aff id="A50">Medical Research Council Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Wareham, Nick J" sort="Wareham, Nick J" uniqKey="Wareham N" first="Nick J" last="Wareham">Nick J. Wareham</name><affiliation><nlm:aff id="A50">Medical Research Council Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Brown, Morris J" sort="Brown, Morris J" uniqKey="Brown M" first="Morris J" last="Brown">Morris J. Brown</name><affiliation><nlm:aff id="A4">Clinical Pharmacology, William Harvey Research Institute, Queen Mary University of London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Dominiczak, Anna F" sort="Dominiczak, Anna F" uniqKey="Dominiczak A" first="Anna F" last="Dominiczak">Anna F. Dominiczak</name><affiliation><nlm:aff id="A95">Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK</nlm:aff></affiliation></author><author><name sortKey="Connell, John M" sort="Connell, John M" uniqKey="Connell J" first="John M" last="Connell">John M. Connell</name><affiliation><nlm:aff id="A39">Medical Research Institute, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK</nlm:aff></affiliation></author><author><name sortKey="Jukema, J Wouter" sort="Jukema, J Wouter" uniqKey="Jukema J" first="J Wouter" last="Jukema">J Wouter Jukema</name><affiliation><nlm:aff id="A64">Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A96">The Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Sattar, Naveed" sort="Sattar, Naveed" uniqKey="Sattar N" first="Naveed" last="Sattar">Naveed Sattar</name><affiliation><nlm:aff id="A95">Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK</nlm:aff></affiliation></author><author><name sortKey="Ford, Ian" sort="Ford, Ian" uniqKey="Ford I" first="Ian" last="Ford">Ian Ford</name><affiliation><nlm:aff id="A61">University of Glasgow, Glasgow, UK</nlm:aff></affiliation></author><author><name sortKey="Packard, Chris J" sort="Packard, Chris J" uniqKey="Packard C" first="Chris J" last="Packard">Chris J. Packard</name><affiliation><nlm:aff id="A61">University of Glasgow, Glasgow, UK</nlm:aff></affiliation></author><author><name sortKey="Esko, T Nu" sort="Esko, T Nu" uniqKey="Esko T" first="T Nu" last="Esko">T Nu Esko</name><affiliation><nlm:aff id="A22">Estonian Genome Center, University of Tartu, Tartu, Estonia</nlm:aff></affiliation><affiliation><nlm:aff id="A97">Division of Endocrinology, Boston Children’s Hospital, Boston, Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A8">Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A9">Program in Medical and Population Genetics, Broad Institute, 7 Cambridge Center, Cambridge, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="M Gi, Reedik" sort="M Gi, Reedik" uniqKey="M Gi R" first="Reedik" last="M Gi">Reedik M Gi</name><affiliation><nlm:aff id="A22">Estonian Genome Center, University of Tartu, Tartu, Estonia</nlm:aff></affiliation></author><author><name sortKey="Metspalu, Andres" sort="Metspalu, Andres" uniqKey="Metspalu A" first="Andres" last="Metspalu">Andres Metspalu</name><affiliation><nlm:aff id="A22">Estonian Genome Center, University of Tartu, Tartu, Estonia</nlm:aff></affiliation><affiliation><nlm:aff id="A98">Institute of Molecular and Cell Biology, Tartu, Estonia</nlm:aff></affiliation></author><author><name sortKey="De Boer, Rudolf A" sort="De Boer, Rudolf A" uniqKey="De Boer R" first="Rudolf A" last="De Boer">Rudolf A. De Boer</name><affiliation><nlm:aff id="A99">Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Van Der Meer, Peter" sort="Van Der Meer, Peter" uniqKey="Van Der Meer P" first="Peter" last="Van Der Meer">Peter Van Der Meer</name><affiliation><nlm:aff id="A99">Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Van Der Harst, Pim" sort="Van Der Harst, Pim" uniqKey="Van Der Harst P" first="Pim" last="Van Der Harst">Pim Van Der Harst</name><affiliation><nlm:aff id="A99">Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A100">Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A101">Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Gambaro, Giovanni" sort="Gambaro, Giovanni" uniqKey="Gambaro G" first="Giovanni" last="Gambaro">Giovanni Gambaro</name><affiliation><nlm:aff id="A102">Division of Nephrology, Department of Internal Medicine and Medical Specialties, Columbus - Gemelli University Hospital, Catholic University, Rome, Italy</nlm:aff></affiliation></author><author><name sortKey="Ingelsson, Erik" sort="Ingelsson, Erik" uniqKey="Ingelsson E" first="Erik" last="Ingelsson">Erik Ingelsson</name><affiliation><nlm:aff id="A103">Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden</nlm:aff></affiliation><affiliation><nlm:aff id="A104">Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California, USA</nlm:aff></affiliation></author><author><name sortKey="Lind, Lars" sort="Lind, Lars" uniqKey="Lind L" first="Lars" last="Lind">Lars Lind</name><affiliation><nlm:aff id="A103">Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden</nlm:aff></affiliation></author><author><name sortKey="De Bakker, Paul Iw" sort="De Bakker, Paul Iw" uniqKey="De Bakker P" first="Paul Iw" last="De Bakker">Paul Iw De Bakker</name><affiliation><nlm:aff id="A105">Department of Medical Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A106">Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Numans, Mattijs E" sort="Numans, Mattijs E" uniqKey="Numans M" first="Mattijs E" last="Numans">Mattijs E. Numans</name><affiliation><nlm:aff id="A107">Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A106">Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Brandslund, Ivan" sort="Brandslund, Ivan" uniqKey="Brandslund I" first="Ivan" last="Brandslund">Ivan Brandslund</name><affiliation><nlm:aff id="A108">Department of Clinical Biochemistry, Lillebaelt Hospital, Vejle, Denmark</nlm:aff></affiliation><affiliation><nlm:aff id="A109">Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark</nlm:aff></affiliation></author><author><name sortKey="Christensen, Cramer" sort="Christensen, Cramer" uniqKey="Christensen C" first="Cramer" last="Christensen">Cramer Christensen</name><affiliation><nlm:aff id="A110">Medical Department, Lillebaelt Hospital, Vejle, Denmark</nlm:aff></affiliation></author><author><name sortKey="Petersen, Eva Rb" sort="Petersen, Eva Rb" uniqKey="Petersen E" first="Eva Rb" last="Petersen">Eva Rb Petersen</name><affiliation><nlm:aff id="A111">Department of Clinical Immunology and Biochemistry, Lillebaelt Hospital, Vejle, Denmark</nlm:aff></affiliation></author><author><name sortKey="Korpi Hyov Lti, Eeva" sort="Korpi Hyov Lti, Eeva" uniqKey="Korpi Hyov Lti E" first="Eeva" last="Korpi-Hyöv Lti">Eeva Korpi-Hyöv Lti</name><affiliation><nlm:aff id="A112">South Ostrobothnia Central Hospital, Seinäjoki, Finland</nlm:aff></affiliation></author><author><name sortKey="Oksa, Heikki" sort="Oksa, Heikki" uniqKey="Oksa H" first="Heikki" last="Oksa">Heikki Oksa</name><affiliation><nlm:aff id="A113">Tampere University Hospital, Tampere, Finland</nlm:aff></affiliation></author><author><name sortKey="Chambers, John C" sort="Chambers, John C" uniqKey="Chambers J" first="John C" last="Chambers">John C. Chambers</name><affiliation><nlm:aff id="A48">Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A49">Department of Cardiology, Ealing Hospital, Middlesex, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A114">Imperial College Healthcare NHS Trust, London, UK</nlm:aff></affiliation></author><author><name sortKey="Kooner, Jaspal S" sort="Kooner, Jaspal S" uniqKey="Kooner J" first="Jaspal S" last="Kooner">Jaspal S. Kooner</name><affiliation><nlm:aff id="A49">Department of Cardiology, Ealing Hospital, Middlesex, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A115">National Heart and Lung Institute, Imperial College London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A114">Imperial College Healthcare NHS Trust, London, UK</nlm:aff></affiliation></author><author><name sortKey="Blakemore, Alexandra If" sort="Blakemore, Alexandra If" uniqKey="Blakemore A" first="Alexandra If" last="Blakemore">Alexandra If Blakemore</name><affiliation><nlm:aff id="A42">Section of Investigative Medicine, Imperial College London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A43">Department of Life Sciences, Brunel University London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Franks, Steve" sort="Franks, Steve" uniqKey="Franks S" first="Steve" last="Franks">Steve Franks</name><affiliation><nlm:aff id="A116">Institute of Reproductive and Developmental Biology, Imperial College London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Jarvelin, Marjo Riitta" sort="Jarvelin, Marjo Riitta" uniqKey="Jarvelin M" first="Marjo-Riitta" last="Jarvelin">Marjo-Riitta Jarvelin</name><affiliation><nlm:aff id="A117">Department of Epidemiology and Biostatistics, Medical Research Council Public Health England Centre for Environment and Health, School of Public Health, Faculty of Medicine, Imperial College London, St. Mary’s Campus, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A118">Centre for Life Course Epidemiology, Faculty of Medicine, University of Oulu, Oulu, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A119">Biocenter Oulu, University of Oulu, Oulu, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A120">Unit of Primary Care, Oulu University Hospital, Oulu, Finland</nlm:aff></affiliation></author><author><name sortKey="Husemoen, Lise L" sort="Husemoen, Lise L" uniqKey="Husemoen L" first="Lise L" last="Husemoen">Lise L. Husemoen</name><affiliation><nlm:aff id="A121">Research Centre for Prevention and Health, Capital Region of Denmark, Copenhagen, Denmark</nlm:aff></affiliation></author><author><name sortKey="Linneberg, Allan" sort="Linneberg, Allan" uniqKey="Linneberg A" first="Allan" last="Linneberg">Allan Linneberg</name><affiliation><nlm:aff id="A121">Research Centre for Prevention and Health, Capital Region of Denmark, Copenhagen, Denmark</nlm:aff></affiliation><affiliation><nlm:aff id="A122">Department of Clinical Experimental Research, Glostrup University Hospital, Glostrup, Denmark</nlm:aff></affiliation><affiliation><nlm:aff id="A123">Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark</nlm:aff></affiliation></author><author><name sortKey="Skaaby, Tea" sort="Skaaby, Tea" uniqKey="Skaaby T" first="Tea" last="Skaaby">Tea Skaaby</name><affiliation><nlm:aff id="A121">Research Centre for Prevention and Health, Capital Region of Denmark, Copenhagen, Denmark</nlm:aff></affiliation></author><author><name sortKey="Thuesen, Betina" sort="Thuesen, Betina" uniqKey="Thuesen B" first="Betina" last="Thuesen">Betina Thuesen</name><affiliation><nlm:aff id="A121">Research Centre for Prevention and Health, Capital Region of Denmark, Copenhagen, Denmark</nlm:aff></affiliation></author><author><name sortKey="Karpe, Fredrik" sort="Karpe, Fredrik" uniqKey="Karpe F" first="Fredrik" last="Karpe">Fredrik Karpe</name><affiliation><nlm:aff id="A40">Oxford Centre for Diabetes, Endocrinology, and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A41">National Institute for Health Research Oxford Biomedical Research Centre, Oxford University Hospital Trusts, Oxford, UK</nlm:aff></affiliation></author><author><name sortKey="Tuomilehto, Jaakko" sort="Tuomilehto, Jaakko" uniqKey="Tuomilehto J" first="Jaakko" last="Tuomilehto">Jaakko Tuomilehto</name><affiliation><nlm:aff id="A36">Department of Health, National Institute for Health and Welfare, Helsinki, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A124">Dasman Diabetes Institute, Dasman, Kuwait</nlm:aff></affiliation><affiliation><nlm:aff id="A125">Centre for Vascular Prevention, Danube-University Krems, Krems, Austria</nlm:aff></affiliation><affiliation><nlm:aff id="A126">King Abdulaziz University, Jeddah, Saudi Arabia</nlm:aff></affiliation></author><author><name sortKey="Doney, Alex Sf" sort="Doney, Alex Sf" uniqKey="Doney A" first="Alex Sf" last="Doney">Alex Sf Doney</name><affiliation><nlm:aff id="A39">Medical Research Institute, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK</nlm:aff></affiliation></author><author><name sortKey="Morris, Andrew D" sort="Morris, Andrew D" uniqKey="Morris A" first="Andrew D" last="Morris">Andrew D. Morris</name><affiliation><nlm:aff id="A127">School of Molecular, Genetic and Population Health Sciences, University of Edinburgh, Medical School, Teviot Place, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Palmer, Colin Na" sort="Palmer, Colin Na" uniqKey="Palmer C" first="Colin Na" last="Palmer">Colin Na Palmer</name><affiliation><nlm:aff id="A39">Medical Research Institute, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK</nlm:aff></affiliation></author><author><name sortKey="Holmen, Oddgeir Lingaas" sort="Holmen, Oddgeir Lingaas" uniqKey="Holmen O" first="Oddgeir Lingaas" last="Holmen">Oddgeir Lingaas Holmen</name><affiliation><nlm:aff id="A128">HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger, Norway</nlm:aff></affiliation><affiliation><nlm:aff id="A129">St. Olav Hospital, Trondheim University Hospital, Trondheim, Norway</nlm:aff></affiliation></author><author><name sortKey="Hveem, Kristian" sort="Hveem, Kristian" uniqKey="Hveem K" first="Kristian" last="Hveem">Kristian Hveem</name><affiliation><nlm:aff id="A128">HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger, Norway</nlm:aff></affiliation><affiliation><nlm:aff id="A130">Department of Medicine, Levanger Hospital, Nord- Trøndelag Health Trust, Levanger, Norway</nlm:aff></affiliation></author><author><name sortKey="Willer, Cristen J" sort="Willer, Cristen J" uniqKey="Willer C" first="Cristen J" last="Willer">Cristen J. Willer</name><affiliation><nlm:aff id="A38">Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A131">Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A132">Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, USA</nlm:aff></affiliation></author><author><name sortKey="Tuomi, Tiinamaija" sort="Tuomi, Tiinamaija" uniqKey="Tuomi T" first="Tiinamaija" last="Tuomi">Tiinamaija Tuomi</name><affiliation><nlm:aff id="A133">Folkhälsan Research Centre, Helsinki, Finland; Department of Endocrinology, Helsinki University Central Hospital, Helsinki, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A134">Institute for Molecular Medicine Finland University of Helsinki, Helsinki, Finland</nlm:aff></affiliation></author><author><name sortKey="Groop, Leif" sort="Groop, Leif" uniqKey="Groop L" first="Leif" last="Groop">Leif Groop</name><affiliation><nlm:aff id="A135">Department of Clinical Sciences, Diabetes and Endocrinology, Lund University Diabetes Centre, Malmö, Sweden</nlm:aff></affiliation><affiliation><nlm:aff id="A134">Institute for Molecular Medicine Finland University of Helsinki, Helsinki, Finland</nlm:aff></affiliation></author><author><name sortKey="K R J M Ki, Annemari" sort="K R J M Ki, Annemari" uniqKey="K R J M Ki A" first="Annemari" last="K R J M Ki">Annemari K R J M Ki</name><affiliation><nlm:aff id="A136">Department of Primary Health Care, Vaasa Central Hospital, Vaasa, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A137">Diabetes Center, Vaasa Health Care Center, Vaasa, Finland</nlm:aff></affiliation></author><author><name sortKey="Palotie, Aarno" sort="Palotie, Aarno" uniqKey="Palotie A" first="Aarno" last="Palotie">Aarno Palotie</name><affiliation><nlm:aff id="A16">Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A9">Program in Medical and Population Genetics, Broad Institute, 7 Cambridge Center, Cambridge, Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A134">Institute for Molecular Medicine Finland University of Helsinki, Helsinki, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A138">Psychiatric and Neurodevelopmental Genetics Unit, Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Ripatti, Samuli" sort="Ripatti, Samuli" uniqKey="Ripatti S" first="Samuli" last="Ripatti">Samuli Ripatti</name><affiliation><nlm:aff id="A134">Institute for Molecular Medicine Finland University of Helsinki, Helsinki, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A139">Department of Public Health, University of Helsinki, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A30">Wellcome Trust Sanger Institute, Genome Campus, Hinxton, UK</nlm:aff></affiliation></author><author><name sortKey="Salomaa, Veikko" sort="Salomaa, Veikko" uniqKey="Salomaa V" first="Veikko" last="Salomaa">Veikko Salomaa</name><affiliation><nlm:aff id="A36">Department of Health, National Institute for Health and Welfare, Helsinki, Finland</nlm:aff></affiliation></author><author><name sortKey="Alam, Dewan S" sort="Alam, Dewan S" uniqKey="Alam D" first="Dewan S" last="Alam">Dewan S. Alam</name><affiliation><nlm:aff id="A140">ICDDR, B; Mohakhali, Dhaka, Bangladesh</nlm:aff></affiliation></author><author><name sortKey="Shafi Majumder, Abdulla Al" sort="Shafi Majumder, Abdulla Al" uniqKey="Shafi Majumder A" first="Abdulla Al" last="Shafi Majumder">Abdulla Al Shafi Majumder</name><affiliation><nlm:aff id="A141">National Institute of Cardiovascular Diseases, Sher-e-Bangla Nagar, Dhaka, Bangladesh</nlm:aff></affiliation></author><author><name sortKey="Di Angelantonio, Emanuele" sort="Di Angelantonio, Emanuele" uniqKey="Di Angelantonio E" first="Emanuele" last="Di Angelantonio">Emanuele Di Angelantonio</name><affiliation><nlm:aff id="A1">Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A54">The National Institute for Health Research Blood and Transplant Research Unit in Donor Health and Genomics, University of Cambridge, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Chowdhury, Rajiv" sort="Chowdhury, Rajiv" uniqKey="Chowdhury R" first="Rajiv" last="Chowdhury">Rajiv Chowdhury</name><affiliation><nlm:aff id="A1">Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Mccarthy, Mark I" sort="Mccarthy, Mark I" uniqKey="Mccarthy M" first="Mark I" last="Mccarthy">Mark I. Mccarthy</name><affiliation><nlm:aff id="A40">Oxford Centre for Diabetes, Endocrinology, and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A41">National Institute for Health Research Oxford Biomedical Research Centre, Oxford University Hospital Trusts, Oxford, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A20">Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK</nlm:aff></affiliation></author><author><name sortKey="Poulter, Neil" sort="Poulter, Neil" uniqKey="Poulter N" first="Neil" last="Poulter">Neil Poulter</name><affiliation><nlm:aff id="A142">International Centre for Circulatory Health, Imperial College London, UK</nlm:aff></affiliation></author><author><name sortKey="Stanton, Alice V" sort="Stanton, Alice V" uniqKey="Stanton A" first="Alice V" last="Stanton">Alice V. Stanton</name><affiliation><nlm:aff id="A143">Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland</nlm:aff></affiliation></author><author><name sortKey="Sever, Peter" sort="Sever, Peter" uniqKey="Sever P" first="Peter" last="Sever">Peter Sever</name><affiliation><nlm:aff id="A142">International Centre for Circulatory Health, Imperial College London, UK</nlm:aff></affiliation></author><author><name sortKey="Amouyel, Philippe" sort="Amouyel, Philippe" uniqKey="Amouyel P" first="Philippe" last="Amouyel">Philippe Amouyel</name><affiliation><nlm:aff id="A144">University of Lille, UMR1167, Risk Factors and Molecular Determinants of aging-related diseases, Lille, France</nlm:aff></affiliation><affiliation><nlm:aff id="A145">Inserm, Lille, France</nlm:aff></affiliation><affiliation><nlm:aff id="A146">Centre Hospitalier Universitaire Lille, Public Health, Lille, France</nlm:aff></affiliation><affiliation><nlm:aff id="A147">Institut Pasteur de Lille, Lille, France</nlm:aff></affiliation></author><author><name sortKey="Arveiler, Dominique" sort="Arveiler, Dominique" uniqKey="Arveiler D" first="Dominique" last="Arveiler">Dominique Arveiler</name><affiliation><nlm:aff id="A148">Department of Epidemiology and Public Health, EA 3430, University of Strasbourg, Strasbourg, France</nlm:aff></affiliation></author><author><name sortKey="Blankenberg, Stefan" sort="Blankenberg, Stefan" uniqKey="Blankenberg S" first="Stefan" last="Blankenberg">Stefan Blankenberg</name><affiliation><nlm:aff id="A149">Department of General and Interventional Cardiology, University Heart Center Hamburg, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A150">University Medical Center Hamburg-Eppendorf, Hamburg, Germany</nlm:aff></affiliation></author><author><name sortKey="Ferrieres, Jean" sort="Ferrieres, Jean" uniqKey="Ferrieres J" first="Jean" last="Ferrières">Jean Ferrières</name><affiliation><nlm:aff id="A151">Department of Epidemiology, UMR 1027- INSERM, Toulouse University-CHU Toulouse, Toulouse, France</nlm:aff></affiliation></author><author><name sortKey="Kee, Frank" sort="Kee, Frank" uniqKey="Kee F" first="Frank" last="Kee">Frank Kee</name><affiliation><nlm:aff id="A152">Director, UKCRC Centre of Excellence for Public Health, Queens University, Belfast, Northern Ireland</nlm:aff></affiliation></author><author><name sortKey="Kuulasmaa, Kari" sort="Kuulasmaa, Kari" uniqKey="Kuulasmaa K" first="Kari" last="Kuulasmaa">Kari Kuulasmaa</name><affiliation><nlm:aff id="A36">Department of Health, National Institute for Health and Welfare, Helsinki, Finland</nlm:aff></affiliation></author><author><name sortKey="Muller Nurasyid, Martina" sort="Muller Nurasyid, Martina" uniqKey="Muller Nurasyid M" first="Martina" last="Müller-Nurasyid">Martina Müller-Nurasyid</name><affiliation><nlm:aff id="A153">Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A154">Department of Medicine I, University Hospital Grosshadern, Ludwig-Maximilians-Universität, Munich, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A155">DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany</nlm:aff></affiliation></author><author><name sortKey="Veronesi, Giovanni" sort="Veronesi, Giovanni" uniqKey="Veronesi G" first="Giovanni" last="Veronesi">Giovanni Veronesi</name><affiliation><nlm:aff id="A156">Research Center in Epidemiology and Preventive Medicine, Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy</nlm:aff></affiliation></author><author><name sortKey="Virtamo, Jarmo" sort="Virtamo, Jarmo" uniqKey="Virtamo J" first="Jarmo" last="Virtamo">Jarmo Virtamo</name><affiliation><nlm:aff id="A36">Department of Health, National Institute for Health and Welfare, Helsinki, Finland</nlm:aff></affiliation></author><author><name sortKey="Deloukas, Panos" sort="Deloukas, Panos" uniqKey="Deloukas P" first="Panos" last="Deloukas">Panos Deloukas</name><affiliation><nlm:aff id="A21">Heart Centre, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A157">Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah, Saudi Arabia</nlm:aff></affiliation></author><author><name sortKey="Elliott, Paul" sort="Elliott, Paul" uniqKey="Elliott P" first="Paul" last="Elliott">Paul Elliott</name><affiliation><nlm:aff id="A117">Department of Epidemiology and Biostatistics, Medical Research Council Public Health England Centre for Environment and Health, School of Public Health, Faculty of Medicine, Imperial College London, St. Mary’s Campus, London, UK</nlm:aff></affiliation></author><author><name sortKey="Zeggini, Eleftheria" sort="Zeggini, Eleftheria" uniqKey="Zeggini E" first="Eleftheria" last="Zeggini">Eleftheria Zeggini</name><affiliation><nlm:aff id="A30">Wellcome Trust Sanger Institute, Genome Campus, Hinxton, UK</nlm:aff></affiliation></author><author><name sortKey="Kathiresan, Sekar" sort="Kathiresan, Sekar" uniqKey="Kathiresan S" first="Sekar" last="Kathiresan">Sekar Kathiresan</name><affiliation><nlm:aff id="A56">Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A158">Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A159">Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A9">Program in Medical and Population Genetics, Broad Institute, 7 Cambridge Center, Cambridge, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Melander, Olle" sort="Melander, Olle" uniqKey="Melander O" first="Olle" last="Melander">Olle Melander</name><affiliation><nlm:aff id="A33">University of Lund, Department of Clinical Sciences, Malmö, Sweden</nlm:aff></affiliation></author><author><name sortKey="Kuusisto, Johanna" sort="Kuusisto, Johanna" uniqKey="Kuusisto J" first="Johanna" last="Kuusisto">Johanna Kuusisto</name><affiliation><nlm:aff id="A32">Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland</nlm:aff></affiliation></author><author><name sortKey="Laakso, Markku" sort="Laakso, Markku" uniqKey="Laakso M" first="Markku" last="Laakso">Markku Laakso</name><affiliation><nlm:aff id="A32">Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland</nlm:aff></affiliation></author><author><name sortKey="Padmanabhan, Sandosh" sort="Padmanabhan, Sandosh" uniqKey="Padmanabhan S" first="Sandosh" last="Padmanabhan">Sandosh Padmanabhan</name><affiliation><nlm:aff id="A95">Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK</nlm:aff></affiliation></author><author><name sortKey="Porteous, David" sort="Porteous, David" uniqKey="Porteous D" first="David" last="Porteous">David Porteous</name><affiliation><nlm:aff id="A66">Centre for Genomic and Experimental Medicine, Medical Research Council Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Hayward, Caroline" sort="Hayward, Caroline" uniqKey="Hayward C" first="Caroline" last="Hayward">Caroline Hayward</name><affiliation><nlm:aff id="A31">Medical Research Council Human Genetics Unit, Medical Research Council Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Scotland, Generation" sort="Scotland, Generation" uniqKey="Scotland G" first="Generation" last="Scotland">Generation Scotland</name><affiliation><nlm:aff id="A160">A Collaboration between the University Medical Schools and NHS, Aberdeen, Dundee, Edinburgh and Glasgow, UK</nlm:aff></affiliation></author><author><name sortKey="Collins, Francis S" sort="Collins, Francis S" uniqKey="Collins F" first="Francis S" last="Collins">Francis S. Collins</name><affiliation><nlm:aff id="A29">Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA</nlm:aff></affiliation></author><author><name sortKey="Mohlke, Karen L" sort="Mohlke, Karen L" uniqKey="Mohlke K" first="Karen L" last="Mohlke">Karen L. Mohlke</name><affiliation><nlm:aff id="A161">Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA</nlm:aff></affiliation></author><author><name sortKey="Hansen, Torben" sort="Hansen, Torben" uniqKey="Hansen T" first="Torben" last="Hansen">Torben Hansen</name><affiliation><nlm:aff id="A11">The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark</nlm:aff></affiliation></author><author><name sortKey="Pedersen, Oluf" sort="Pedersen, Oluf" uniqKey="Pedersen O" first="Oluf" last="Pedersen">Oluf Pedersen</name><affiliation><nlm:aff id="A11">The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark</nlm:aff></affiliation></author><author><name sortKey="Boehnke, Michael" sort="Boehnke, Michael" uniqKey="Boehnke M" first="Michael" last="Boehnke">Michael Boehnke</name><affiliation><nlm:aff id="A13">Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A12">Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA</nlm:aff></affiliation></author><author><name sortKey="Stringham, Heather M" sort="Stringham, Heather M" uniqKey="Stringham H" first="Heather M" last="Stringham">Heather M. Stringham</name><affiliation><nlm:aff id="A13">Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A12">Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA</nlm:aff></affiliation></author><author><name sortKey="Frossard, Philippe" sort="Frossard, Philippe" uniqKey="Frossard P" first="Philippe" last="Frossard">Philippe Frossard</name><affiliation><nlm:aff id="A27">Centre for Non-Communicable Diseases, Karachi, Pakistan</nlm:aff></affiliation></author><author><name sortKey="Newton Cheh, Christopher" sort="Newton Cheh, Christopher" uniqKey="Newton Cheh C" first="Christopher" last="Newton-Cheh">Christopher Newton-Cheh</name><affiliation><nlm:aff id="A56">Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A158">Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Tobin, Martin D" sort="Tobin, Martin D" uniqKey="Tobin M" first="Martin D" last="Tobin">Martin D. Tobin</name><affiliation><nlm:aff id="A6">Department of Health Sciences, University of Leicester, Leicester, UK</nlm:aff></affiliation></author><author><name sortKey="Nordestgaard, B Rge Gr Nne" sort="Nordestgaard, B Rge Gr Nne" uniqKey="Nordestgaard B" first="B Rge Gr Nne" last="Nordestgaard">B Rge Gr Nne Nordestgaard</name><affiliation><nlm:aff id="A26">Department of Clinical Biochemistry Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark</nlm:aff></affiliation></author><author><name sortKey="Caulfield, Mark J" sort="Caulfield, Mark J" uniqKey="Caulfield M" first="Mark J" last="Caulfield">Mark J. Caulfield</name><affiliation><nlm:aff id="A4">Clinical Pharmacology, William Harvey Research Institute, Queen Mary University of London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A5">National Institute for Health Research Barts Cardiovascular Biomedical Research Unit, Queen Mary University of London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Mahajan, Anubha" sort="Mahajan, Anubha" uniqKey="Mahajan A" first="Anubha" last="Mahajan">Anubha Mahajan</name><affiliation><nlm:aff id="A20">Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK</nlm:aff></affiliation></author><author><name sortKey="Morris, Andrew P" sort="Morris, Andrew P" uniqKey="Morris A" first="Andrew P" last="Morris">Andrew P. Morris</name><affiliation><nlm:aff id="A20">Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A7">Department of Biostatistics, University of Liverpool, Liverpool, UK</nlm:aff></affiliation></author><author><name sortKey="Tomaszewski, Maciej" sort="Tomaszewski, Maciej" uniqKey="Tomaszewski M" first="Maciej" last="Tomaszewski">Maciej Tomaszewski</name><affiliation><nlm:aff id="A18">Department of Cardiovascular Sciences, University of Leicester, Leicester, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A19">National Institute for Health Research Leicester Biomedical Research Unit in Cardiovascular Disease, Leicester, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A162">Institute of Cardiovascular Sciences, University of Manchester, Manchester, UK</nlm:aff></affiliation></author><author><name sortKey="Samani, Nilesh J" sort="Samani, Nilesh J" uniqKey="Samani N" first="Nilesh J" last="Samani">Nilesh J. Samani</name><affiliation><nlm:aff id="A18">Department of Cardiovascular Sciences, University of Leicester, Leicester, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A19">National Institute for Health Research Leicester Biomedical Research Unit in Cardiovascular Disease, Leicester, UK</nlm:aff></affiliation></author><author><name sortKey="Saleheen, Danish" sort="Saleheen, Danish" uniqKey="Saleheen D" first="Danish" last="Saleheen">Danish Saleheen</name><affiliation><nlm:aff id="A28">Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A27">Centre for Non-Communicable Diseases, Karachi, Pakistan</nlm:aff></affiliation><affiliation><nlm:aff id="A1">Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Asselbergs, Folkert W" sort="Asselbergs, Folkert W" uniqKey="Asselbergs F" first="Folkert W" last="Asselbergs">Folkert W. Asselbergs</name><affiliation><nlm:aff id="A15">Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A101">Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A163">Faculty of Population Health Sciences, Institute of Cardiovascular Science, University College London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Lindgren, Cecilia M" sort="Lindgren, Cecilia M" uniqKey="Lindgren C" first="Cecilia M" last="Lindgren">Cecilia M. Lindgren</name><affiliation><nlm:aff id="A164">The Big Data Institute at the Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A9">Program in Medical and Population Genetics, Broad Institute, 7 Cambridge Center, Cambridge, Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A20">Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK</nlm:aff></affiliation></author><author><name sortKey="Danesh, John" sort="Danesh, John" uniqKey="Danesh J" first="John" last="Danesh">John Danesh</name><affiliation><nlm:aff id="A1">Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A165">Wellcome Trust Sanger Institute, Hinxton, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A54">The National Institute for Health Research Blood and Transplant Research Unit in Donor Health and Genomics, University of Cambridge, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Wain, Louise V" sort="Wain, Louise V" uniqKey="Wain L" first="Louise V" last="Wain">Louise V. Wain</name><affiliation><nlm:aff id="A6">Department of Health Sciences, University of Leicester, Leicester, UK</nlm:aff></affiliation></author><author><name sortKey="Butterworth, Adam S" sort="Butterworth, Adam S" uniqKey="Butterworth A" first="Adam S" last="Butterworth">Adam S. Butterworth</name><affiliation><nlm:aff id="A1">Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A166">The National Institute for Health Research Blood and Transplant Research</nlm:aff></affiliation></author><author><name sortKey="Howson, Joanna Mm" sort="Howson, Joanna Mm" uniqKey="Howson J" first="Joanna Mm" last="Howson">Joanna Mm Howson</name><affiliation><nlm:aff id="A1">Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Munroe, Patricia B" sort="Munroe, Patricia B" uniqKey="Munroe P" first="Patricia B" last="Munroe">Patricia B. Munroe</name><affiliation><nlm:aff id="A4">Clinical Pharmacology, William Harvey Research Institute, Queen Mary University of London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A5">National Institute for Health Research Barts Cardiovascular Biomedical Research Unit, Queen Mary University of London, London, UK</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">27618447</idno><idno type="pmc">5056636</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5056636</idno><idno type="RBID">PMC:5056636</idno><idno type="doi">10.1038/ng.3654</idno><date when="2016">2016</date><idno type="wicri:Area/Pmc/Corpus">002E47</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002E47</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension</title><author><name sortKey="Surendran, Praveen" sort="Surendran, Praveen" uniqKey="Surendran P" first="Praveen" last="Surendran">Praveen Surendran</name><affiliation><nlm:aff id="A1">Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Drenos, Fotios" sort="Drenos, Fotios" uniqKey="Drenos F" first="Fotios" last="Drenos">Fotios Drenos</name><affiliation><nlm:aff id="A2">Medical Research Council Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A3">Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, Rayne Building University College London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Young, Robin" sort="Young, Robin" uniqKey="Young R" first="Robin" last="Young">Robin Young</name><affiliation><nlm:aff id="A1">Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Warren, Helen" sort="Warren, Helen" uniqKey="Warren H" first="Helen" last="Warren">Helen Warren</name><affiliation><nlm:aff id="A4">Clinical Pharmacology, William Harvey Research Institute, Queen Mary University of London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A5">National Institute for Health Research Barts Cardiovascular Biomedical Research Unit, Queen Mary University of London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Cook, James P" sort="Cook, James P" uniqKey="Cook J" first="James P" last="Cook">James P. Cook</name><affiliation><nlm:aff id="A6">Department of Health Sciences, University of Leicester, Leicester, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A7">Department of Biostatistics, University of Liverpool, Liverpool, UK</nlm:aff></affiliation></author><author><name sortKey="Manning, Alisa K" sort="Manning, Alisa K" uniqKey="Manning A" first="Alisa K" last="Manning">Alisa K. Manning</name><affiliation><nlm:aff id="A8">Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A9">Program in Medical and Population Genetics, Broad Institute, 7 Cambridge Center, Cambridge, Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A10">Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Grarup, Niels" sort="Grarup, Niels" uniqKey="Grarup N" first="Niels" last="Grarup">Niels Grarup</name><affiliation><nlm:aff id="A11">The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark</nlm:aff></affiliation></author><author><name sortKey="Sim, Xueling" sort="Sim, Xueling" uniqKey="Sim X" first="Xueling" last="Sim">Xueling Sim</name><affiliation><nlm:aff id="A12">Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A13">Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A14">Saw Swee Hock School of Public Health, National University of Singapore, National University Health System, Singapore</nlm:aff></affiliation></author><author><name sortKey="Barnes, Daniel R" sort="Barnes, Daniel R" uniqKey="Barnes D" first="Daniel R" last="Barnes">Daniel R. Barnes</name><affiliation><nlm:aff id="A1">Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Witkowska, Kate" sort="Witkowska, Kate" uniqKey="Witkowska K" first="Kate" last="Witkowska">Kate Witkowska</name><affiliation><nlm:aff id="A4">Clinical Pharmacology, William Harvey Research Institute, Queen Mary University of London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A5">National Institute for Health Research Barts Cardiovascular Biomedical Research Unit, Queen Mary University of London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Staley, James R" sort="Staley, James R" uniqKey="Staley J" first="James R" last="Staley">James R. Staley</name><affiliation><nlm:aff id="A1">Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Tragante, Vinicius" sort="Tragante, Vinicius" uniqKey="Tragante V" first="Vinicius" last="Tragante">Vinicius Tragante</name><affiliation><nlm:aff id="A15">Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Tukiainen, Taru" sort="Tukiainen, Taru" uniqKey="Tukiainen T" first="Taru" last="Tukiainen">Taru Tukiainen</name><affiliation><nlm:aff id="A8">Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A9">Program in Medical and Population Genetics, Broad Institute, 7 Cambridge Center, Cambridge, Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A16">Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Yaghootkar, Hanieh" sort="Yaghootkar, Hanieh" uniqKey="Yaghootkar H" first="Hanieh" last="Yaghootkar">Hanieh Yaghootkar</name><affiliation><nlm:aff id="A17">Genetics of Complex Traits, Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK</nlm:aff></affiliation></author><author><name sortKey="Masca, Nicholas" sort="Masca, Nicholas" uniqKey="Masca N" first="Nicholas" last="Masca">Nicholas Masca</name><affiliation><nlm:aff id="A18">Department of Cardiovascular Sciences, University of Leicester, Leicester, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A19">National Institute for Health Research Leicester Biomedical Research Unit in Cardiovascular Disease, Leicester, UK</nlm:aff></affiliation></author><author><name sortKey="Freitag, Daniel F" sort="Freitag, Daniel F" uniqKey="Freitag D" first="Daniel F" last="Freitag">Daniel F. Freitag</name><affiliation><nlm:aff id="A1">Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Ferreira, Teresa" sort="Ferreira, Teresa" uniqKey="Ferreira T" first="Teresa" last="Ferreira">Teresa Ferreira</name><affiliation><nlm:aff id="A20">Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK</nlm:aff></affiliation></author><author><name sortKey="Giannakopoulou, Olga" sort="Giannakopoulou, Olga" uniqKey="Giannakopoulou O" first="Olga" last="Giannakopoulou">Olga Giannakopoulou</name><affiliation><nlm:aff id="A21">Heart Centre, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Tinker, Andrew" sort="Tinker, Andrew" uniqKey="Tinker A" first="Andrew" last="Tinker">Andrew Tinker</name><affiliation><nlm:aff id="A21">Heart Centre, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A5">National Institute for Health Research Barts Cardiovascular Biomedical Research Unit, Queen Mary University of London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Harakalova, Magdalena" sort="Harakalova, Magdalena" uniqKey="Harakalova M" first="Magdalena" last="Harakalova">Magdalena Harakalova</name><affiliation><nlm:aff id="A15">Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Mihailov, Evelin" sort="Mihailov, Evelin" uniqKey="Mihailov E" first="Evelin" last="Mihailov">Evelin Mihailov</name><affiliation><nlm:aff id="A22">Estonian Genome Center, University of Tartu, Tartu, Estonia</nlm:aff></affiliation></author><author><name sortKey="Liu, Chunyu" sort="Liu, Chunyu" uniqKey="Liu C" first="Chunyu" last="Liu">Chunyu Liu</name><affiliation><nlm:aff id="A23">National Heart, Lung, and Blood Institute’s and Boston University’s Framingham Heart Study, Framingham, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Kraja, Aldi T" sort="Kraja, Aldi T" uniqKey="Kraja A" first="Aldi T" last="Kraja">Aldi T. Kraja</name><affiliation><nlm:aff id="A24">Division of Statistical Genomics, Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, Missouri, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A25">Department of Genetics, Washington University School of Medicine, St. Louis, Missouri, USA</nlm:aff></affiliation></author><author><name sortKey="Fallgaard Nielsen, Sune" sort="Fallgaard Nielsen, Sune" uniqKey="Fallgaard Nielsen S" first="Sune" last="Fallgaard Nielsen">Sune Fallgaard Nielsen</name><affiliation><nlm:aff id="A26">Department of Clinical Biochemistry Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark</nlm:aff></affiliation></author><author><name sortKey="Rasheed, Asif" sort="Rasheed, Asif" uniqKey="Rasheed A" first="Asif" last="Rasheed">Asif Rasheed</name><affiliation><nlm:aff id="A27">Centre for Non-Communicable Diseases, Karachi, Pakistan</nlm:aff></affiliation></author><author><name sortKey="Samuel, Maria" sort="Samuel, Maria" uniqKey="Samuel M" first="Maria" last="Samuel">Maria Samuel</name><affiliation><nlm:aff id="A27">Centre for Non-Communicable Diseases, Karachi, Pakistan</nlm:aff></affiliation></author><author><name sortKey="Zhao, Wei" sort="Zhao, Wei" uniqKey="Zhao W" first="Wei" last="Zhao">Wei Zhao</name><affiliation><nlm:aff id="A28">Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA</nlm:aff></affiliation></author><author><name sortKey="Bonnycastle, Lori L" sort="Bonnycastle, Lori L" uniqKey="Bonnycastle L" first="Lori L" last="Bonnycastle">Lori L. Bonnycastle</name><affiliation><nlm:aff id="A29">Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA</nlm:aff></affiliation></author><author><name sortKey="Jackson, Anne U" sort="Jackson, Anne U" uniqKey="Jackson A" first="Anne U" last="Jackson">Anne U. Jackson</name><affiliation><nlm:aff id="A13">Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A12">Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA</nlm:aff></affiliation></author><author><name sortKey="Narisu, Narisu" sort="Narisu, Narisu" uniqKey="Narisu N" first="Narisu" last="Narisu">Narisu Narisu</name><affiliation><nlm:aff id="A29">Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA</nlm:aff></affiliation></author><author><name sortKey="Swift, Amy J" sort="Swift, Amy J" uniqKey="Swift A" first="Amy J" last="Swift">Amy J. Swift</name><affiliation><nlm:aff id="A29">Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA</nlm:aff></affiliation></author><author><name sortKey="Southam, Lorraine" sort="Southam, Lorraine" uniqKey="Southam L" first="Lorraine" last="Southam">Lorraine Southam</name><affiliation><nlm:aff id="A30">Wellcome Trust Sanger Institute, Genome Campus, Hinxton, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A20">Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK</nlm:aff></affiliation></author><author><name sortKey="Marten, Jonathan" sort="Marten, Jonathan" uniqKey="Marten J" first="Jonathan" last="Marten">Jonathan Marten</name><affiliation><nlm:aff id="A31">Medical Research Council Human Genetics Unit, Medical Research Council Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Huyghe, Jeroen R" sort="Huyghe, Jeroen R" uniqKey="Huyghe J" first="Jeroen R" last="Huyghe">Jeroen R. Huyghe</name><affiliation><nlm:aff id="A13">Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A12">Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA</nlm:aff></affiliation></author><author><name sortKey="Stan Kova, Alena" sort="Stan Kova, Alena" uniqKey="Stan Kova A" first="Alena" last="Stan Ková">Alena Stan Ková</name><affiliation><nlm:aff id="A32">Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland</nlm:aff></affiliation></author><author><name sortKey="Fava, Cristiano" sort="Fava, Cristiano" uniqKey="Fava C" first="Cristiano" last="Fava">Cristiano Fava</name><affiliation><nlm:aff id="A33">University of Lund, Department of Clinical Sciences, Malmö, Sweden</nlm:aff></affiliation><affiliation><nlm:aff id="A34">University of Verona, Department of Medicine, Verona, Italy</nlm:aff></affiliation></author><author><name sortKey="Ohlsson, Therese" sort="Ohlsson, Therese" uniqKey="Ohlsson T" first="Therese" last="Ohlsson">Therese Ohlsson</name><affiliation><nlm:aff id="A33">University of Lund, Department of Clinical Sciences, Malmö, Sweden</nlm:aff></affiliation></author><author><name sortKey="Matchan, Angela" sort="Matchan, Angela" uniqKey="Matchan A" first="Angela" last="Matchan">Angela Matchan</name><affiliation><nlm:aff id="A30">Wellcome Trust Sanger Institute, Genome Campus, Hinxton, UK</nlm:aff></affiliation></author><author><name sortKey="Stirrups, Kathleen E" sort="Stirrups, Kathleen E" uniqKey="Stirrups K" first="Kathleen E" last="Stirrups">Kathleen E. Stirrups</name><affiliation><nlm:aff id="A21">Heart Centre, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A35">Department of Haematology, University of Cambridge, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Bork Jensen, Jette" sort="Bork Jensen, Jette" uniqKey="Bork Jensen J" first="Jette" last="Bork-Jensen">Jette Bork-Jensen</name><affiliation><nlm:aff id="A11">The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark</nlm:aff></affiliation></author><author><name sortKey="Gjesing, Anette P" sort="Gjesing, Anette P" uniqKey="Gjesing A" first="Anette P" last="Gjesing">Anette P. Gjesing</name><affiliation><nlm:aff id="A11">The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark</nlm:aff></affiliation></author><author><name sortKey="Kontto, Jukka" sort="Kontto, Jukka" uniqKey="Kontto J" first="Jukka" last="Kontto">Jukka Kontto</name><affiliation><nlm:aff id="A36">Department of Health, National Institute for Health and Welfare, Helsinki, Finland</nlm:aff></affiliation></author><author><name sortKey="Perola, Markus" sort="Perola, Markus" uniqKey="Perola M" first="Markus" last="Perola">Markus Perola</name><affiliation><nlm:aff id="A36">Department of Health, National Institute for Health and Welfare, Helsinki, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A37">Institute of Molecular Medicine FIMM, University of Helsinki, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A22">Estonian Genome Center, University of Tartu, Tartu, Estonia</nlm:aff></affiliation></author><author><name sortKey="Shaw Hawkins, Susan" sort="Shaw Hawkins, Susan" uniqKey="Shaw Hawkins S" first="Susan" last="Shaw-Hawkins">Susan Shaw-Hawkins</name><affiliation><nlm:aff id="A4">Clinical Pharmacology, William Harvey Research Institute, Queen Mary University of London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Havulinna, Aki S" sort="Havulinna, Aki S" uniqKey="Havulinna A" first="Aki S" last="Havulinna">Aki S. Havulinna</name><affiliation><nlm:aff id="A36">Department of Health, National Institute for Health and Welfare, Helsinki, Finland</nlm:aff></affiliation></author><author><name sortKey="Zhang, He" sort="Zhang, He" uniqKey="Zhang H" first="He" last="Zhang">He Zhang</name><affiliation><nlm:aff id="A38">Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan, USA</nlm:aff></affiliation></author><author><name sortKey="Donnelly, Louise A" sort="Donnelly, Louise A" uniqKey="Donnelly L" first="Louise A" last="Donnelly">Louise A. Donnelly</name><affiliation><nlm:aff id="A39">Medical Research Institute, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK</nlm:aff></affiliation></author><author><name sortKey="Groves, Christopher J" sort="Groves, Christopher J" uniqKey="Groves C" first="Christopher J" last="Groves">Christopher J. Groves</name><affiliation><nlm:aff id="A40">Oxford Centre for Diabetes, Endocrinology, and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK</nlm:aff></affiliation></author><author><name sortKey="Rayner, N William" sort="Rayner, N William" uniqKey="Rayner N" first="N William" last="Rayner">N William Rayner</name><affiliation><nlm:aff id="A40">Oxford Centre for Diabetes, Endocrinology, and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A20">Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A30">Wellcome Trust Sanger Institute, Genome Campus, Hinxton, UK</nlm:aff></affiliation></author><author><name sortKey="Neville, Matt J" sort="Neville, Matt J" uniqKey="Neville M" first="Matt J" last="Neville">Matt J. Neville</name><affiliation><nlm:aff id="A40">Oxford Centre for Diabetes, Endocrinology, and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A41">National Institute for Health Research Oxford Biomedical Research Centre, Oxford University Hospital Trusts, Oxford, UK</nlm:aff></affiliation></author><author><name sortKey="Robertson, Neil R" sort="Robertson, Neil R" uniqKey="Robertson N" first="Neil R" last="Robertson">Neil R. Robertson</name><affiliation><nlm:aff id="A20">Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A40">Oxford Centre for Diabetes, Endocrinology, and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK</nlm:aff></affiliation></author><author><name sortKey="Yiorkas, Andrianos M" sort="Yiorkas, Andrianos M" uniqKey="Yiorkas A" first="Andrianos M" last="Yiorkas">Andrianos M. Yiorkas</name><affiliation><nlm:aff id="A42">Section of Investigative Medicine, Imperial College London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A43">Department of Life Sciences, Brunel University London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Herzig, Karl Heinz" sort="Herzig, Karl Heinz" uniqKey="Herzig K" first="Karl-Heinz" last="Herzig">Karl-Heinz Herzig</name><affiliation><nlm:aff id="A44">Institute of Biomedicine, Biocenter Oulu, University of Oulu, Oulu, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A45">Department of Gastroenterology and Metabolism, Poznan University of Medical Sciences, Poznan, Poland</nlm:aff></affiliation></author><author><name sortKey="Kajantie, Eero" sort="Kajantie, Eero" uniqKey="Kajantie E" first="Eero" last="Kajantie">Eero Kajantie</name><affiliation><nlm:aff id="A36">Department of Health, National Institute for Health and Welfare, Helsinki, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A46">Hospital for Children and Adolescents, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A47">Department of Obstetrics and Gynaecology, Oulu University Hospital and University of Oulu, Oulu, Finland</nlm:aff></affiliation></author><author><name sortKey="Zhang, Weihua" sort="Zhang, Weihua" uniqKey="Zhang W" first="Weihua" last="Zhang">Weihua Zhang</name><affiliation><nlm:aff id="A48">Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A49">Department of Cardiology, Ealing Hospital, Middlesex, UK</nlm:aff></affiliation></author><author><name sortKey="Willems, Sara M" sort="Willems, Sara M" uniqKey="Willems S" first="Sara M" last="Willems">Sara M. Willems</name><affiliation><nlm:aff id="A50">Medical Research Council Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Lannfelt, Lars" sort="Lannfelt, Lars" uniqKey="Lannfelt L" first="Lars" last="Lannfelt">Lars Lannfelt</name><affiliation><nlm:aff id="A51">Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden</nlm:aff></affiliation></author><author><name sortKey="Malerba, Giovanni" sort="Malerba, Giovanni" uniqKey="Malerba G" first="Giovanni" last="Malerba">Giovanni Malerba</name><affiliation><nlm:aff id="A52">Section of Biology and Genetics, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy</nlm:aff></affiliation></author><author><name sortKey="Soranzo, Nicole" sort="Soranzo, Nicole" uniqKey="Soranzo N" first="Nicole" last="Soranzo">Nicole Soranzo</name><affiliation><nlm:aff id="A53">Human Genetics, Wellcome Trust Sanger Institute, Hinxton, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A35">Department of Haematology, University of Cambridge, Cambridge, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A54">The National Institute for Health Research Blood and Transplant Research Unit in Donor Health and Genomics, University of Cambridge, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Trabetti, Elisabetta" sort="Trabetti, Elisabetta" uniqKey="Trabetti E" first="Elisabetta" last="Trabetti">Elisabetta Trabetti</name><affiliation><nlm:aff id="A52">Section of Biology and Genetics, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy</nlm:aff></affiliation></author><author><name sortKey="Verweij, Niek" sort="Verweij, Niek" uniqKey="Verweij N" first="Niek" last="Verweij">Niek Verweij</name><affiliation><nlm:aff id="A55">University Medical Center Groningen, University of Groningen, Department of Cardiology, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A9">Program in Medical and Population Genetics, Broad Institute, 7 Cambridge Center, Cambridge, Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A56">Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Evangelou, Evangelos" sort="Evangelou, Evangelos" uniqKey="Evangelou E" first="Evangelos" last="Evangelou">Evangelos Evangelou</name><affiliation><nlm:aff id="A48">Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A57">Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece</nlm:aff></affiliation></author><author><name sortKey="Moayyeri, Alireza" sort="Moayyeri, Alireza" uniqKey="Moayyeri A" first="Alireza" last="Moayyeri">Alireza Moayyeri</name><affiliation><nlm:aff id="A48">Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A58">Farr Institute of Health Informatics Research, Institute of Health Informatics, University College London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Vergnaud, Anne Claire" sort="Vergnaud, Anne Claire" uniqKey="Vergnaud A" first="Anne-Claire" last="Vergnaud">Anne-Claire Vergnaud</name><affiliation><nlm:aff id="A48">Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Nelson, Christopher P" sort="Nelson, Christopher P" uniqKey="Nelson C" first="Christopher P" last="Nelson">Christopher P. Nelson</name><affiliation><nlm:aff id="A18">Department of Cardiovascular Sciences, University of Leicester, Leicester, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A19">National Institute for Health Research Leicester Biomedical Research Unit in Cardiovascular Disease, Leicester, UK</nlm:aff></affiliation></author><author><name sortKey="Poveda, Alaitz" sort="Poveda, Alaitz" uniqKey="Poveda A" first="Alaitz" last="Poveda">Alaitz Poveda</name><affiliation><nlm:aff id="A59">Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, Sweden</nlm:aff></affiliation><affiliation><nlm:aff id="A60">Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Bilbao, Spain</nlm:aff></affiliation></author><author><name sortKey="Varga, Tibor V" sort="Varga, Tibor V" uniqKey="Varga T" first="Tibor V" last="Varga">Tibor V. Varga</name><affiliation><nlm:aff id="A59">Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, Sweden</nlm:aff></affiliation></author><author><name sortKey="Caslake, Muriel" sort="Caslake, Muriel" uniqKey="Caslake M" first="Muriel" last="Caslake">Muriel Caslake</name><affiliation><nlm:aff id="A61">University of Glasgow, Glasgow, UK</nlm:aff></affiliation></author><author><name sortKey="De Craen, Anton Jm" sort="De Craen, Anton Jm" uniqKey="De Craen A" first="Anton Jm" last="De Craen">Anton Jm De Craen</name><affiliation><nlm:aff id="A62">Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A63">Mr. De Craen suddenly passed away January 2016</nlm:aff></affiliation></author><author><name sortKey="Trompet, Stella" sort="Trompet, Stella" uniqKey="Trompet S" first="Stella" last="Trompet">Stella Trompet</name><affiliation><nlm:aff id="A62">Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A64">Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Luan, Jian N" sort="Luan, Jian N" uniqKey="Luan J" first="Jian N" last="Luan">Jian N Luan</name><affiliation><nlm:aff id="A50">Medical Research Council Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Scott, Robert A" sort="Scott, Robert A" uniqKey="Scott R" first="Robert A" last="Scott">Robert A. Scott</name><affiliation><nlm:aff id="A50">Medical Research Council Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Harris, Sarah E" sort="Harris, Sarah E" uniqKey="Harris S" first="Sarah E" last="Harris">Sarah E. Harris</name><affiliation><nlm:aff id="A65">Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A66">Centre for Genomic and Experimental Medicine, Medical Research Council Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Liewald, David Cm" sort="Liewald, David Cm" uniqKey="Liewald D" first="David Cm" last="Liewald">David Cm Liewald</name><affiliation><nlm:aff id="A65">Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A67">Department of Psychology, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Marioni, Riccardo" sort="Marioni, Riccardo" uniqKey="Marioni R" first="Riccardo" last="Marioni">Riccardo Marioni</name><affiliation><nlm:aff id="A65">Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A66">Centre for Genomic and Experimental Medicine, Medical Research Council Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A68">Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia</nlm:aff></affiliation></author><author><name sortKey="Menni, Cristina" sort="Menni, Cristina" uniqKey="Menni C" first="Cristina" last="Menni">Cristina Menni</name><affiliation><nlm:aff id="A69">Department of Twin Research and Genetic Epidemiology, King’s College London, UK</nlm:aff></affiliation></author><author><name sortKey="Farmaki, Aliki Eleni" sort="Farmaki, Aliki Eleni" uniqKey="Farmaki A" first="Aliki-Eleni" last="Farmaki">Aliki-Eleni Farmaki</name><affiliation><nlm:aff id="A70">Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece</nlm:aff></affiliation></author><author><name sortKey="Hallmans, Goran" sort="Hallmans, Goran" uniqKey="Hallmans G" first="Göran" last="Hallmans">Göran Hallmans</name><affiliation><nlm:aff id="A71">Department of Biobank Research, Umeå University, Umeå, Sweden</nlm:aff></affiliation></author><author><name sortKey="Renstrom, Frida" sort="Renstrom, Frida" uniqKey="Renstrom F" first="Frida" last="Renström">Frida Renström</name><affiliation><nlm:aff id="A59">Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, Sweden</nlm:aff></affiliation><affiliation><nlm:aff id="A71">Department of Biobank Research, Umeå University, Umeå, Sweden</nlm:aff></affiliation></author><author><name sortKey="Huffman, Jennifer E" sort="Huffman, Jennifer E" uniqKey="Huffman J" first="Jennifer E" last="Huffman">Jennifer E. Huffman</name><affiliation><nlm:aff id="A31">Medical Research Council Human Genetics Unit, Medical Research Council Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A23">National Heart, Lung, and Blood Institute’s and Boston University’s Framingham Heart Study, Framingham, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Hassinen, Maija" sort="Hassinen, Maija" uniqKey="Hassinen M" first="Maija" last="Hassinen">Maija Hassinen</name><affiliation><nlm:aff id="A72">Kuopio Research Institute of Exercise Medicine, Kuopio, Finland</nlm:aff></affiliation></author><author><name sortKey="Burgess, Stephen" sort="Burgess, Stephen" uniqKey="Burgess S" first="Stephen" last="Burgess">Stephen Burgess</name><affiliation><nlm:aff id="A1">Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Vasan, Ramachandran S" sort="Vasan, Ramachandran S" uniqKey="Vasan R" first="Ramachandran S" last="Vasan">Ramachandran S. Vasan</name><affiliation><nlm:aff id="A23">National Heart, Lung, and Blood Institute’s and Boston University’s Framingham Heart Study, Framingham, Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A73">Section of Cardiology, Department of Medicine, Boston University Schools of Medicine and Public Health, Boston, Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A74">Sections of Preventive Medicine and Epidemiology, Department of Medicine, Boston University Schools of Medicine and Public Health, Boston, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Felix, Janine F" sort="Felix, Janine F" uniqKey="Felix J" first="Janine F" last="Felix">Janine F. Felix</name><affiliation><nlm:aff id="A75">Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Uria Nickelsen, Maria" sort="Uria Nickelsen, Maria" uniqKey="Uria Nickelsen M" first="Maria" last="Uria-Nickelsen">Maria Uria-Nickelsen</name><affiliation><nlm:aff id="A77">Development Management and Planning, Pfizer Worldwide Research and Development</nlm:aff></affiliation></author><author><name sortKey="Malarstig, Anders" sort="Malarstig, Anders" uniqKey="Malarstig A" first="Anders" last="Malarstig">Anders Malarstig</name><affiliation><nlm:aff id="A78">Pfizer Worldwide Research and Development, Stockholm, Sweden</nlm:aff></affiliation></author><author><name sortKey="Reily, Dermot F" sort="Reily, Dermot F" uniqKey="Reily D" first="Dermot F" last="Reily">Dermot F. Reily</name><affiliation><nlm:aff id="A79">Merck Research Laboratories, Genetics and Pharmacogenomics, Boston, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Hoek, Maarten" sort="Hoek, Maarten" uniqKey="Hoek M" first="Maarten" last="Hoek">Maarten Hoek</name><affiliation><nlm:aff id="A80">Merck Research Laboratories, Cardiometabolic Disease, Kenilworth, New Jersey, USA</nlm:aff></affiliation></author><author><name sortKey="Vogt, Thomas" sort="Vogt, Thomas" uniqKey="Vogt T" first="Thomas" last="Vogt">Thomas Vogt</name><affiliation><nlm:aff id="A80">Merck Research Laboratories, Cardiometabolic Disease, Kenilworth, New Jersey, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A81">CHDI Management/CHDI Foundation, Princeton, New Jersey, USA</nlm:aff></affiliation></author><author><name sortKey="Lin, Honghuang" sort="Lin, Honghuang" uniqKey="Lin H" first="Honghuang" last="Lin">Honghuang Lin</name><affiliation><nlm:aff id="A23">National Heart, Lung, and Blood Institute’s and Boston University’s Framingham Heart Study, Framingham, Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A82">Section of Computational Biomedicine, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Lieb, Wolfgang" sort="Lieb, Wolfgang" uniqKey="Lieb W" first="Wolfgang" last="Lieb">Wolfgang Lieb</name><affiliation><nlm:aff id="A83">Institute of Epidemiology and Biobank Popgen, Kiel University, Kiel, Germany</nlm:aff></affiliation></author><author><name sortKey="Traylor, Matthew" sort="Traylor, Matthew" uniqKey="Traylor M" first="Matthew" last="Traylor">Matthew Traylor</name><affiliation><nlm:aff id="A84">Neurology Unit, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Markus, Hugh F" sort="Markus, Hugh F" uniqKey="Markus H" first="Hugh F" last="Markus">Hugh F. Markus</name><affiliation><nlm:aff id="A84">Neurology Unit, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Highland, Heather M" sort="Highland, Heather M" uniqKey="Highland H" first="Heather M" last="Highland">Heather M. Highland</name><affiliation><nlm:aff id="A85">University of North Carolina at Chapel Hill, Department of Epidemiology, Chapel Hill, North Carolina, USA</nlm:aff></affiliation></author><author><name sortKey="Justice, Anne E" sort="Justice, Anne E" uniqKey="Justice A" first="Anne E" last="Justice">Anne E. Justice</name><affiliation><nlm:aff id="A85">University of North Carolina at Chapel Hill, Department of Epidemiology, Chapel Hill, North Carolina, USA</nlm:aff></affiliation></author><author><name sortKey="Marouli, Eirini" sort="Marouli, Eirini" uniqKey="Marouli E" first="Eirini" last="Marouli">Eirini Marouli</name><affiliation><nlm:aff id="A21">Heart Centre, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Lindstrom, Jaana" sort="Lindstrom, Jaana" uniqKey="Lindstrom J" first="Jaana" last="Lindström">Jaana Lindström</name><affiliation><nlm:aff id="A36">Department of Health, National Institute for Health and Welfare, Helsinki, Finland</nlm:aff></affiliation></author><author><name sortKey="Uusitupa, Matti" sort="Uusitupa, Matti" uniqKey="Uusitupa M" first="Matti" last="Uusitupa">Matti Uusitupa</name><affiliation><nlm:aff id="A86">Department of Public Health and Clinical Nutrition, University of Eastern Finland, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A87">Research Unit, Kuopio University Hospital, Kuopio, Finland</nlm:aff></affiliation></author><author><name sortKey="Komulainen, Pirjo" sort="Komulainen, Pirjo" uniqKey="Komulainen P" first="Pirjo" last="Komulainen">Pirjo Komulainen</name><affiliation><nlm:aff id="A72">Kuopio Research Institute of Exercise Medicine, Kuopio, Finland</nlm:aff></affiliation></author><author><name sortKey="Lakka, Timo A" sort="Lakka, Timo A" uniqKey="Lakka T" first="Timo A" last="Lakka">Timo A. Lakka</name><affiliation><nlm:aff id="A72">Kuopio Research Institute of Exercise Medicine, Kuopio, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A88">Institute of Biomedicine/Physiology, University of Eastern Finland, Kuopio Campus, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A89">Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland</nlm:aff></affiliation></author><author><name sortKey="Rauramaa, Rainer" sort="Rauramaa, Rainer" uniqKey="Rauramaa R" first="Rainer" last="Rauramaa">Rainer Rauramaa</name><affiliation><nlm:aff id="A72">Kuopio Research Institute of Exercise Medicine, Kuopio, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A89">Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland</nlm:aff></affiliation></author><author><name sortKey="Polasek, Ozren" sort="Polasek, Ozren" uniqKey="Polasek O" first="Ozren" last="Polasek">Ozren Polasek</name><affiliation><nlm:aff id="A90">Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A91">Faculty of Medicine, University of Split, Croatia</nlm:aff></affiliation></author><author><name sortKey="Rudan, Igor" sort="Rudan, Igor" uniqKey="Rudan I" first="Igor" last="Rudan">Igor Rudan</name><affiliation><nlm:aff id="A90">Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Rolandsson, Olov" sort="Rolandsson, Olov" uniqKey="Rolandsson O" first="Olov" last="Rolandsson">Olov Rolandsson</name><affiliation><nlm:aff id="A92">Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden</nlm:aff></affiliation></author><author><name sortKey="Franks, Paul W" sort="Franks, Paul W" uniqKey="Franks P" first="Paul W" last="Franks">Paul W. Franks</name><affiliation><nlm:aff id="A59">Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, Sweden</nlm:aff></affiliation><affiliation><nlm:aff id="A92">Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden</nlm:aff></affiliation><affiliation><nlm:aff id="A93">Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Dedoussis, George" sort="Dedoussis, George" uniqKey="Dedoussis G" first="George" last="Dedoussis">George Dedoussis</name><affiliation><nlm:aff id="A70">Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece</nlm:aff></affiliation></author><author><name sortKey="Spector, Timothy D" sort="Spector, Timothy D" uniqKey="Spector T" first="Timothy D" last="Spector">Timothy D. Spector</name><affiliation><nlm:aff id="A69">Department of Twin Research and Genetic Epidemiology, King’s College London, UK</nlm:aff></affiliation></author><author><name sortKey="Jousilahti, Pekka" sort="Jousilahti, Pekka" uniqKey="Jousilahti P" first="Pekka" last="Jousilahti">Pekka Jousilahti</name><affiliation><nlm:aff id="A36">Department of Health, National Institute for Health and Welfare, Helsinki, Finland</nlm:aff></affiliation></author><author><name sortKey="M Nnisto, Satu" sort="M Nnisto, Satu" uniqKey="M Nnisto S" first="Satu" last="M Nnistö">Satu M Nnistö</name><affiliation><nlm:aff id="A36">Department of Health, National Institute for Health and Welfare, Helsinki, Finland</nlm:aff></affiliation></author><author><name sortKey="Deary, Ian J" sort="Deary, Ian J" uniqKey="Deary I" first="Ian J" last="Deary">Ian J. Deary</name><affiliation><nlm:aff id="A65">Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A67">Department of Psychology, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Starr, John M" sort="Starr, John M" uniqKey="Starr J" first="John M" last="Starr">John M. Starr</name><affiliation><nlm:aff id="A65">Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A94">Alzheimer Scotland Research Centre, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Langenberg, Claudia" sort="Langenberg, Claudia" uniqKey="Langenberg C" first="Claudia" last="Langenberg">Claudia Langenberg</name><affiliation><nlm:aff id="A50">Medical Research Council Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Wareham, Nick J" sort="Wareham, Nick J" uniqKey="Wareham N" first="Nick J" last="Wareham">Nick J. Wareham</name><affiliation><nlm:aff id="A50">Medical Research Council Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Brown, Morris J" sort="Brown, Morris J" uniqKey="Brown M" first="Morris J" last="Brown">Morris J. Brown</name><affiliation><nlm:aff id="A4">Clinical Pharmacology, William Harvey Research Institute, Queen Mary University of London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Dominiczak, Anna F" sort="Dominiczak, Anna F" uniqKey="Dominiczak A" first="Anna F" last="Dominiczak">Anna F. Dominiczak</name><affiliation><nlm:aff id="A95">Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK</nlm:aff></affiliation></author><author><name sortKey="Connell, John M" sort="Connell, John M" uniqKey="Connell J" first="John M" last="Connell">John M. Connell</name><affiliation><nlm:aff id="A39">Medical Research Institute, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK</nlm:aff></affiliation></author><author><name sortKey="Jukema, J Wouter" sort="Jukema, J Wouter" uniqKey="Jukema J" first="J Wouter" last="Jukema">J Wouter Jukema</name><affiliation><nlm:aff id="A64">Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A96">The Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Sattar, Naveed" sort="Sattar, Naveed" uniqKey="Sattar N" first="Naveed" last="Sattar">Naveed Sattar</name><affiliation><nlm:aff id="A95">Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK</nlm:aff></affiliation></author><author><name sortKey="Ford, Ian" sort="Ford, Ian" uniqKey="Ford I" first="Ian" last="Ford">Ian Ford</name><affiliation><nlm:aff id="A61">University of Glasgow, Glasgow, UK</nlm:aff></affiliation></author><author><name sortKey="Packard, Chris J" sort="Packard, Chris J" uniqKey="Packard C" first="Chris J" last="Packard">Chris J. Packard</name><affiliation><nlm:aff id="A61">University of Glasgow, Glasgow, UK</nlm:aff></affiliation></author><author><name sortKey="Esko, T Nu" sort="Esko, T Nu" uniqKey="Esko T" first="T Nu" last="Esko">T Nu Esko</name><affiliation><nlm:aff id="A22">Estonian Genome Center, University of Tartu, Tartu, Estonia</nlm:aff></affiliation><affiliation><nlm:aff id="A97">Division of Endocrinology, Boston Children’s Hospital, Boston, Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A8">Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A9">Program in Medical and Population Genetics, Broad Institute, 7 Cambridge Center, Cambridge, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="M Gi, Reedik" sort="M Gi, Reedik" uniqKey="M Gi R" first="Reedik" last="M Gi">Reedik M Gi</name><affiliation><nlm:aff id="A22">Estonian Genome Center, University of Tartu, Tartu, Estonia</nlm:aff></affiliation></author><author><name sortKey="Metspalu, Andres" sort="Metspalu, Andres" uniqKey="Metspalu A" first="Andres" last="Metspalu">Andres Metspalu</name><affiliation><nlm:aff id="A22">Estonian Genome Center, University of Tartu, Tartu, Estonia</nlm:aff></affiliation><affiliation><nlm:aff id="A98">Institute of Molecular and Cell Biology, Tartu, Estonia</nlm:aff></affiliation></author><author><name sortKey="De Boer, Rudolf A" sort="De Boer, Rudolf A" uniqKey="De Boer R" first="Rudolf A" last="De Boer">Rudolf A. De Boer</name><affiliation><nlm:aff id="A99">Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Van Der Meer, Peter" sort="Van Der Meer, Peter" uniqKey="Van Der Meer P" first="Peter" last="Van Der Meer">Peter Van Der Meer</name><affiliation><nlm:aff id="A99">Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Van Der Harst, Pim" sort="Van Der Harst, Pim" uniqKey="Van Der Harst P" first="Pim" last="Van Der Harst">Pim Van Der Harst</name><affiliation><nlm:aff id="A99">Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A100">Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A101">Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Gambaro, Giovanni" sort="Gambaro, Giovanni" uniqKey="Gambaro G" first="Giovanni" last="Gambaro">Giovanni Gambaro</name><affiliation><nlm:aff id="A102">Division of Nephrology, Department of Internal Medicine and Medical Specialties, Columbus - Gemelli University Hospital, Catholic University, Rome, Italy</nlm:aff></affiliation></author><author><name sortKey="Ingelsson, Erik" sort="Ingelsson, Erik" uniqKey="Ingelsson E" first="Erik" last="Ingelsson">Erik Ingelsson</name><affiliation><nlm:aff id="A103">Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden</nlm:aff></affiliation><affiliation><nlm:aff id="A104">Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California, USA</nlm:aff></affiliation></author><author><name sortKey="Lind, Lars" sort="Lind, Lars" uniqKey="Lind L" first="Lars" last="Lind">Lars Lind</name><affiliation><nlm:aff id="A103">Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden</nlm:aff></affiliation></author><author><name sortKey="De Bakker, Paul Iw" sort="De Bakker, Paul Iw" uniqKey="De Bakker P" first="Paul Iw" last="De Bakker">Paul Iw De Bakker</name><affiliation><nlm:aff id="A105">Department of Medical Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A106">Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Numans, Mattijs E" sort="Numans, Mattijs E" uniqKey="Numans M" first="Mattijs E" last="Numans">Mattijs E. Numans</name><affiliation><nlm:aff id="A107">Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A106">Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Brandslund, Ivan" sort="Brandslund, Ivan" uniqKey="Brandslund I" first="Ivan" last="Brandslund">Ivan Brandslund</name><affiliation><nlm:aff id="A108">Department of Clinical Biochemistry, Lillebaelt Hospital, Vejle, Denmark</nlm:aff></affiliation><affiliation><nlm:aff id="A109">Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark</nlm:aff></affiliation></author><author><name sortKey="Christensen, Cramer" sort="Christensen, Cramer" uniqKey="Christensen C" first="Cramer" last="Christensen">Cramer Christensen</name><affiliation><nlm:aff id="A110">Medical Department, Lillebaelt Hospital, Vejle, Denmark</nlm:aff></affiliation></author><author><name sortKey="Petersen, Eva Rb" sort="Petersen, Eva Rb" uniqKey="Petersen E" first="Eva Rb" last="Petersen">Eva Rb Petersen</name><affiliation><nlm:aff id="A111">Department of Clinical Immunology and Biochemistry, Lillebaelt Hospital, Vejle, Denmark</nlm:aff></affiliation></author><author><name sortKey="Korpi Hyov Lti, Eeva" sort="Korpi Hyov Lti, Eeva" uniqKey="Korpi Hyov Lti E" first="Eeva" last="Korpi-Hyöv Lti">Eeva Korpi-Hyöv Lti</name><affiliation><nlm:aff id="A112">South Ostrobothnia Central Hospital, Seinäjoki, Finland</nlm:aff></affiliation></author><author><name sortKey="Oksa, Heikki" sort="Oksa, Heikki" uniqKey="Oksa H" first="Heikki" last="Oksa">Heikki Oksa</name><affiliation><nlm:aff id="A113">Tampere University Hospital, Tampere, Finland</nlm:aff></affiliation></author><author><name sortKey="Chambers, John C" sort="Chambers, John C" uniqKey="Chambers J" first="John C" last="Chambers">John C. Chambers</name><affiliation><nlm:aff id="A48">Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A49">Department of Cardiology, Ealing Hospital, Middlesex, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A114">Imperial College Healthcare NHS Trust, London, UK</nlm:aff></affiliation></author><author><name sortKey="Kooner, Jaspal S" sort="Kooner, Jaspal S" uniqKey="Kooner J" first="Jaspal S" last="Kooner">Jaspal S. Kooner</name><affiliation><nlm:aff id="A49">Department of Cardiology, Ealing Hospital, Middlesex, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A115">National Heart and Lung Institute, Imperial College London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A114">Imperial College Healthcare NHS Trust, London, UK</nlm:aff></affiliation></author><author><name sortKey="Blakemore, Alexandra If" sort="Blakemore, Alexandra If" uniqKey="Blakemore A" first="Alexandra If" last="Blakemore">Alexandra If Blakemore</name><affiliation><nlm:aff id="A42">Section of Investigative Medicine, Imperial College London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A43">Department of Life Sciences, Brunel University London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Franks, Steve" sort="Franks, Steve" uniqKey="Franks S" first="Steve" last="Franks">Steve Franks</name><affiliation><nlm:aff id="A116">Institute of Reproductive and Developmental Biology, Imperial College London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Jarvelin, Marjo Riitta" sort="Jarvelin, Marjo Riitta" uniqKey="Jarvelin M" first="Marjo-Riitta" last="Jarvelin">Marjo-Riitta Jarvelin</name><affiliation><nlm:aff id="A117">Department of Epidemiology and Biostatistics, Medical Research Council Public Health England Centre for Environment and Health, School of Public Health, Faculty of Medicine, Imperial College London, St. Mary’s Campus, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A118">Centre for Life Course Epidemiology, Faculty of Medicine, University of Oulu, Oulu, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A119">Biocenter Oulu, University of Oulu, Oulu, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A120">Unit of Primary Care, Oulu University Hospital, Oulu, Finland</nlm:aff></affiliation></author><author><name sortKey="Husemoen, Lise L" sort="Husemoen, Lise L" uniqKey="Husemoen L" first="Lise L" last="Husemoen">Lise L. Husemoen</name><affiliation><nlm:aff id="A121">Research Centre for Prevention and Health, Capital Region of Denmark, Copenhagen, Denmark</nlm:aff></affiliation></author><author><name sortKey="Linneberg, Allan" sort="Linneberg, Allan" uniqKey="Linneberg A" first="Allan" last="Linneberg">Allan Linneberg</name><affiliation><nlm:aff id="A121">Research Centre for Prevention and Health, Capital Region of Denmark, Copenhagen, Denmark</nlm:aff></affiliation><affiliation><nlm:aff id="A122">Department of Clinical Experimental Research, Glostrup University Hospital, Glostrup, Denmark</nlm:aff></affiliation><affiliation><nlm:aff id="A123">Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark</nlm:aff></affiliation></author><author><name sortKey="Skaaby, Tea" sort="Skaaby, Tea" uniqKey="Skaaby T" first="Tea" last="Skaaby">Tea Skaaby</name><affiliation><nlm:aff id="A121">Research Centre for Prevention and Health, Capital Region of Denmark, Copenhagen, Denmark</nlm:aff></affiliation></author><author><name sortKey="Thuesen, Betina" sort="Thuesen, Betina" uniqKey="Thuesen B" first="Betina" last="Thuesen">Betina Thuesen</name><affiliation><nlm:aff id="A121">Research Centre for Prevention and Health, Capital Region of Denmark, Copenhagen, Denmark</nlm:aff></affiliation></author><author><name sortKey="Karpe, Fredrik" sort="Karpe, Fredrik" uniqKey="Karpe F" first="Fredrik" last="Karpe">Fredrik Karpe</name><affiliation><nlm:aff id="A40">Oxford Centre for Diabetes, Endocrinology, and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A41">National Institute for Health Research Oxford Biomedical Research Centre, Oxford University Hospital Trusts, Oxford, UK</nlm:aff></affiliation></author><author><name sortKey="Tuomilehto, Jaakko" sort="Tuomilehto, Jaakko" uniqKey="Tuomilehto J" first="Jaakko" last="Tuomilehto">Jaakko Tuomilehto</name><affiliation><nlm:aff id="A36">Department of Health, National Institute for Health and Welfare, Helsinki, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A124">Dasman Diabetes Institute, Dasman, Kuwait</nlm:aff></affiliation><affiliation><nlm:aff id="A125">Centre for Vascular Prevention, Danube-University Krems, Krems, Austria</nlm:aff></affiliation><affiliation><nlm:aff id="A126">King Abdulaziz University, Jeddah, Saudi Arabia</nlm:aff></affiliation></author><author><name sortKey="Doney, Alex Sf" sort="Doney, Alex Sf" uniqKey="Doney A" first="Alex Sf" last="Doney">Alex Sf Doney</name><affiliation><nlm:aff id="A39">Medical Research Institute, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK</nlm:aff></affiliation></author><author><name sortKey="Morris, Andrew D" sort="Morris, Andrew D" uniqKey="Morris A" first="Andrew D" last="Morris">Andrew D. Morris</name><affiliation><nlm:aff id="A127">School of Molecular, Genetic and Population Health Sciences, University of Edinburgh, Medical School, Teviot Place, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Palmer, Colin Na" sort="Palmer, Colin Na" uniqKey="Palmer C" first="Colin Na" last="Palmer">Colin Na Palmer</name><affiliation><nlm:aff id="A39">Medical Research Institute, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK</nlm:aff></affiliation></author><author><name sortKey="Holmen, Oddgeir Lingaas" sort="Holmen, Oddgeir Lingaas" uniqKey="Holmen O" first="Oddgeir Lingaas" last="Holmen">Oddgeir Lingaas Holmen</name><affiliation><nlm:aff id="A128">HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger, Norway</nlm:aff></affiliation><affiliation><nlm:aff id="A129">St. Olav Hospital, Trondheim University Hospital, Trondheim, Norway</nlm:aff></affiliation></author><author><name sortKey="Hveem, Kristian" sort="Hveem, Kristian" uniqKey="Hveem K" first="Kristian" last="Hveem">Kristian Hveem</name><affiliation><nlm:aff id="A128">HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger, Norway</nlm:aff></affiliation><affiliation><nlm:aff id="A130">Department of Medicine, Levanger Hospital, Nord- Trøndelag Health Trust, Levanger, Norway</nlm:aff></affiliation></author><author><name sortKey="Willer, Cristen J" sort="Willer, Cristen J" uniqKey="Willer C" first="Cristen J" last="Willer">Cristen J. Willer</name><affiliation><nlm:aff id="A38">Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A131">Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A132">Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, USA</nlm:aff></affiliation></author><author><name sortKey="Tuomi, Tiinamaija" sort="Tuomi, Tiinamaija" uniqKey="Tuomi T" first="Tiinamaija" last="Tuomi">Tiinamaija Tuomi</name><affiliation><nlm:aff id="A133">Folkhälsan Research Centre, Helsinki, Finland; Department of Endocrinology, Helsinki University Central Hospital, Helsinki, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A134">Institute for Molecular Medicine Finland University of Helsinki, Helsinki, Finland</nlm:aff></affiliation></author><author><name sortKey="Groop, Leif" sort="Groop, Leif" uniqKey="Groop L" first="Leif" last="Groop">Leif Groop</name><affiliation><nlm:aff id="A135">Department of Clinical Sciences, Diabetes and Endocrinology, Lund University Diabetes Centre, Malmö, Sweden</nlm:aff></affiliation><affiliation><nlm:aff id="A134">Institute for Molecular Medicine Finland University of Helsinki, Helsinki, Finland</nlm:aff></affiliation></author><author><name sortKey="K R J M Ki, Annemari" sort="K R J M Ki, Annemari" uniqKey="K R J M Ki A" first="Annemari" last="K R J M Ki">Annemari K R J M Ki</name><affiliation><nlm:aff id="A136">Department of Primary Health Care, Vaasa Central Hospital, Vaasa, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A137">Diabetes Center, Vaasa Health Care Center, Vaasa, Finland</nlm:aff></affiliation></author><author><name sortKey="Palotie, Aarno" sort="Palotie, Aarno" uniqKey="Palotie A" first="Aarno" last="Palotie">Aarno Palotie</name><affiliation><nlm:aff id="A16">Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A9">Program in Medical and Population Genetics, Broad Institute, 7 Cambridge Center, Cambridge, Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A134">Institute for Molecular Medicine Finland University of Helsinki, Helsinki, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A138">Psychiatric and Neurodevelopmental Genetics Unit, Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Ripatti, Samuli" sort="Ripatti, Samuli" uniqKey="Ripatti S" first="Samuli" last="Ripatti">Samuli Ripatti</name><affiliation><nlm:aff id="A134">Institute for Molecular Medicine Finland University of Helsinki, Helsinki, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A139">Department of Public Health, University of Helsinki, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A30">Wellcome Trust Sanger Institute, Genome Campus, Hinxton, UK</nlm:aff></affiliation></author><author><name sortKey="Salomaa, Veikko" sort="Salomaa, Veikko" uniqKey="Salomaa V" first="Veikko" last="Salomaa">Veikko Salomaa</name><affiliation><nlm:aff id="A36">Department of Health, National Institute for Health and Welfare, Helsinki, Finland</nlm:aff></affiliation></author><author><name sortKey="Alam, Dewan S" sort="Alam, Dewan S" uniqKey="Alam D" first="Dewan S" last="Alam">Dewan S. Alam</name><affiliation><nlm:aff id="A140">ICDDR, B; Mohakhali, Dhaka, Bangladesh</nlm:aff></affiliation></author><author><name sortKey="Shafi Majumder, Abdulla Al" sort="Shafi Majumder, Abdulla Al" uniqKey="Shafi Majumder A" first="Abdulla Al" last="Shafi Majumder">Abdulla Al Shafi Majumder</name><affiliation><nlm:aff id="A141">National Institute of Cardiovascular Diseases, Sher-e-Bangla Nagar, Dhaka, Bangladesh</nlm:aff></affiliation></author><author><name sortKey="Di Angelantonio, Emanuele" sort="Di Angelantonio, Emanuele" uniqKey="Di Angelantonio E" first="Emanuele" last="Di Angelantonio">Emanuele Di Angelantonio</name><affiliation><nlm:aff id="A1">Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A54">The National Institute for Health Research Blood and Transplant Research Unit in Donor Health and Genomics, University of Cambridge, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Chowdhury, Rajiv" sort="Chowdhury, Rajiv" uniqKey="Chowdhury R" first="Rajiv" last="Chowdhury">Rajiv Chowdhury</name><affiliation><nlm:aff id="A1">Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Mccarthy, Mark I" sort="Mccarthy, Mark I" uniqKey="Mccarthy M" first="Mark I" last="Mccarthy">Mark I. Mccarthy</name><affiliation><nlm:aff id="A40">Oxford Centre for Diabetes, Endocrinology, and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A41">National Institute for Health Research Oxford Biomedical Research Centre, Oxford University Hospital Trusts, Oxford, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A20">Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK</nlm:aff></affiliation></author><author><name sortKey="Poulter, Neil" sort="Poulter, Neil" uniqKey="Poulter N" first="Neil" last="Poulter">Neil Poulter</name><affiliation><nlm:aff id="A142">International Centre for Circulatory Health, Imperial College London, UK</nlm:aff></affiliation></author><author><name sortKey="Stanton, Alice V" sort="Stanton, Alice V" uniqKey="Stanton A" first="Alice V" last="Stanton">Alice V. Stanton</name><affiliation><nlm:aff id="A143">Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland</nlm:aff></affiliation></author><author><name sortKey="Sever, Peter" sort="Sever, Peter" uniqKey="Sever P" first="Peter" last="Sever">Peter Sever</name><affiliation><nlm:aff id="A142">International Centre for Circulatory Health, Imperial College London, UK</nlm:aff></affiliation></author><author><name sortKey="Amouyel, Philippe" sort="Amouyel, Philippe" uniqKey="Amouyel P" first="Philippe" last="Amouyel">Philippe Amouyel</name><affiliation><nlm:aff id="A144">University of Lille, UMR1167, Risk Factors and Molecular Determinants of aging-related diseases, Lille, France</nlm:aff></affiliation><affiliation><nlm:aff id="A145">Inserm, Lille, France</nlm:aff></affiliation><affiliation><nlm:aff id="A146">Centre Hospitalier Universitaire Lille, Public Health, Lille, France</nlm:aff></affiliation><affiliation><nlm:aff id="A147">Institut Pasteur de Lille, Lille, France</nlm:aff></affiliation></author><author><name sortKey="Arveiler, Dominique" sort="Arveiler, Dominique" uniqKey="Arveiler D" first="Dominique" last="Arveiler">Dominique Arveiler</name><affiliation><nlm:aff id="A148">Department of Epidemiology and Public Health, EA 3430, University of Strasbourg, Strasbourg, France</nlm:aff></affiliation></author><author><name sortKey="Blankenberg, Stefan" sort="Blankenberg, Stefan" uniqKey="Blankenberg S" first="Stefan" last="Blankenberg">Stefan Blankenberg</name><affiliation><nlm:aff id="A149">Department of General and Interventional Cardiology, University Heart Center Hamburg, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A150">University Medical Center Hamburg-Eppendorf, Hamburg, Germany</nlm:aff></affiliation></author><author><name sortKey="Ferrieres, Jean" sort="Ferrieres, Jean" uniqKey="Ferrieres J" first="Jean" last="Ferrières">Jean Ferrières</name><affiliation><nlm:aff id="A151">Department of Epidemiology, UMR 1027- INSERM, Toulouse University-CHU Toulouse, Toulouse, France</nlm:aff></affiliation></author><author><name sortKey="Kee, Frank" sort="Kee, Frank" uniqKey="Kee F" first="Frank" last="Kee">Frank Kee</name><affiliation><nlm:aff id="A152">Director, UKCRC Centre of Excellence for Public Health, Queens University, Belfast, Northern Ireland</nlm:aff></affiliation></author><author><name sortKey="Kuulasmaa, Kari" sort="Kuulasmaa, Kari" uniqKey="Kuulasmaa K" first="Kari" last="Kuulasmaa">Kari Kuulasmaa</name><affiliation><nlm:aff id="A36">Department of Health, National Institute for Health and Welfare, Helsinki, Finland</nlm:aff></affiliation></author><author><name sortKey="Muller Nurasyid, Martina" sort="Muller Nurasyid, Martina" uniqKey="Muller Nurasyid M" first="Martina" last="Müller-Nurasyid">Martina Müller-Nurasyid</name><affiliation><nlm:aff id="A153">Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A154">Department of Medicine I, University Hospital Grosshadern, Ludwig-Maximilians-Universität, Munich, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A155">DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany</nlm:aff></affiliation></author><author><name sortKey="Veronesi, Giovanni" sort="Veronesi, Giovanni" uniqKey="Veronesi G" first="Giovanni" last="Veronesi">Giovanni Veronesi</name><affiliation><nlm:aff id="A156">Research Center in Epidemiology and Preventive Medicine, Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy</nlm:aff></affiliation></author><author><name sortKey="Virtamo, Jarmo" sort="Virtamo, Jarmo" uniqKey="Virtamo J" first="Jarmo" last="Virtamo">Jarmo Virtamo</name><affiliation><nlm:aff id="A36">Department of Health, National Institute for Health and Welfare, Helsinki, Finland</nlm:aff></affiliation></author><author><name sortKey="Deloukas, Panos" sort="Deloukas, Panos" uniqKey="Deloukas P" first="Panos" last="Deloukas">Panos Deloukas</name><affiliation><nlm:aff id="A21">Heart Centre, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A157">Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah, Saudi Arabia</nlm:aff></affiliation></author><author><name sortKey="Elliott, Paul" sort="Elliott, Paul" uniqKey="Elliott P" first="Paul" last="Elliott">Paul Elliott</name><affiliation><nlm:aff id="A117">Department of Epidemiology and Biostatistics, Medical Research Council Public Health England Centre for Environment and Health, School of Public Health, Faculty of Medicine, Imperial College London, St. Mary’s Campus, London, UK</nlm:aff></affiliation></author><author><name sortKey="Zeggini, Eleftheria" sort="Zeggini, Eleftheria" uniqKey="Zeggini E" first="Eleftheria" last="Zeggini">Eleftheria Zeggini</name><affiliation><nlm:aff id="A30">Wellcome Trust Sanger Institute, Genome Campus, Hinxton, UK</nlm:aff></affiliation></author><author><name sortKey="Kathiresan, Sekar" sort="Kathiresan, Sekar" uniqKey="Kathiresan S" first="Sekar" last="Kathiresan">Sekar Kathiresan</name><affiliation><nlm:aff id="A56">Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A158">Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A159">Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A9">Program in Medical and Population Genetics, Broad Institute, 7 Cambridge Center, Cambridge, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Melander, Olle" sort="Melander, Olle" uniqKey="Melander O" first="Olle" last="Melander">Olle Melander</name><affiliation><nlm:aff id="A33">University of Lund, Department of Clinical Sciences, Malmö, Sweden</nlm:aff></affiliation></author><author><name sortKey="Kuusisto, Johanna" sort="Kuusisto, Johanna" uniqKey="Kuusisto J" first="Johanna" last="Kuusisto">Johanna Kuusisto</name><affiliation><nlm:aff id="A32">Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland</nlm:aff></affiliation></author><author><name sortKey="Laakso, Markku" sort="Laakso, Markku" uniqKey="Laakso M" first="Markku" last="Laakso">Markku Laakso</name><affiliation><nlm:aff id="A32">Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland</nlm:aff></affiliation></author><author><name sortKey="Padmanabhan, Sandosh" sort="Padmanabhan, Sandosh" uniqKey="Padmanabhan S" first="Sandosh" last="Padmanabhan">Sandosh Padmanabhan</name><affiliation><nlm:aff id="A95">Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK</nlm:aff></affiliation></author><author><name sortKey="Porteous, David" sort="Porteous, David" uniqKey="Porteous D" first="David" last="Porteous">David Porteous</name><affiliation><nlm:aff id="A66">Centre for Genomic and Experimental Medicine, Medical Research Council Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Hayward, Caroline" sort="Hayward, Caroline" uniqKey="Hayward C" first="Caroline" last="Hayward">Caroline Hayward</name><affiliation><nlm:aff id="A31">Medical Research Council Human Genetics Unit, Medical Research Council Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Scotland, Generation" sort="Scotland, Generation" uniqKey="Scotland G" first="Generation" last="Scotland">Generation Scotland</name><affiliation><nlm:aff id="A160">A Collaboration between the University Medical Schools and NHS, Aberdeen, Dundee, Edinburgh and Glasgow, UK</nlm:aff></affiliation></author><author><name sortKey="Collins, Francis S" sort="Collins, Francis S" uniqKey="Collins F" first="Francis S" last="Collins">Francis S. Collins</name><affiliation><nlm:aff id="A29">Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA</nlm:aff></affiliation></author><author><name sortKey="Mohlke, Karen L" sort="Mohlke, Karen L" uniqKey="Mohlke K" first="Karen L" last="Mohlke">Karen L. Mohlke</name><affiliation><nlm:aff id="A161">Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA</nlm:aff></affiliation></author><author><name sortKey="Hansen, Torben" sort="Hansen, Torben" uniqKey="Hansen T" first="Torben" last="Hansen">Torben Hansen</name><affiliation><nlm:aff id="A11">The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark</nlm:aff></affiliation></author><author><name sortKey="Pedersen, Oluf" sort="Pedersen, Oluf" uniqKey="Pedersen O" first="Oluf" last="Pedersen">Oluf Pedersen</name><affiliation><nlm:aff id="A11">The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark</nlm:aff></affiliation></author><author><name sortKey="Boehnke, Michael" sort="Boehnke, Michael" uniqKey="Boehnke M" first="Michael" last="Boehnke">Michael Boehnke</name><affiliation><nlm:aff id="A13">Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A12">Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA</nlm:aff></affiliation></author><author><name sortKey="Stringham, Heather M" sort="Stringham, Heather M" uniqKey="Stringham H" first="Heather M" last="Stringham">Heather M. Stringham</name><affiliation><nlm:aff id="A13">Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A12">Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA</nlm:aff></affiliation></author><author><name sortKey="Frossard, Philippe" sort="Frossard, Philippe" uniqKey="Frossard P" first="Philippe" last="Frossard">Philippe Frossard</name><affiliation><nlm:aff id="A27">Centre for Non-Communicable Diseases, Karachi, Pakistan</nlm:aff></affiliation></author><author><name sortKey="Newton Cheh, Christopher" sort="Newton Cheh, Christopher" uniqKey="Newton Cheh C" first="Christopher" last="Newton-Cheh">Christopher Newton-Cheh</name><affiliation><nlm:aff id="A56">Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A158">Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Tobin, Martin D" sort="Tobin, Martin D" uniqKey="Tobin M" first="Martin D" last="Tobin">Martin D. Tobin</name><affiliation><nlm:aff id="A6">Department of Health Sciences, University of Leicester, Leicester, UK</nlm:aff></affiliation></author><author><name sortKey="Nordestgaard, B Rge Gr Nne" sort="Nordestgaard, B Rge Gr Nne" uniqKey="Nordestgaard B" first="B Rge Gr Nne" last="Nordestgaard">B Rge Gr Nne Nordestgaard</name><affiliation><nlm:aff id="A26">Department of Clinical Biochemistry Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark</nlm:aff></affiliation></author><author><name sortKey="Caulfield, Mark J" sort="Caulfield, Mark J" uniqKey="Caulfield M" first="Mark J" last="Caulfield">Mark J. Caulfield</name><affiliation><nlm:aff id="A4">Clinical Pharmacology, William Harvey Research Institute, Queen Mary University of London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A5">National Institute for Health Research Barts Cardiovascular Biomedical Research Unit, Queen Mary University of London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Mahajan, Anubha" sort="Mahajan, Anubha" uniqKey="Mahajan A" first="Anubha" last="Mahajan">Anubha Mahajan</name><affiliation><nlm:aff id="A20">Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK</nlm:aff></affiliation></author><author><name sortKey="Morris, Andrew P" sort="Morris, Andrew P" uniqKey="Morris A" first="Andrew P" last="Morris">Andrew P. Morris</name><affiliation><nlm:aff id="A20">Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A7">Department of Biostatistics, University of Liverpool, Liverpool, UK</nlm:aff></affiliation></author><author><name sortKey="Tomaszewski, Maciej" sort="Tomaszewski, Maciej" uniqKey="Tomaszewski M" first="Maciej" last="Tomaszewski">Maciej Tomaszewski</name><affiliation><nlm:aff id="A18">Department of Cardiovascular Sciences, University of Leicester, Leicester, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A19">National Institute for Health Research Leicester Biomedical Research Unit in Cardiovascular Disease, Leicester, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A162">Institute of Cardiovascular Sciences, University of Manchester, Manchester, UK</nlm:aff></affiliation></author><author><name sortKey="Samani, Nilesh J" sort="Samani, Nilesh J" uniqKey="Samani N" first="Nilesh J" last="Samani">Nilesh J. Samani</name><affiliation><nlm:aff id="A18">Department of Cardiovascular Sciences, University of Leicester, Leicester, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A19">National Institute for Health Research Leicester Biomedical Research Unit in Cardiovascular Disease, Leicester, UK</nlm:aff></affiliation></author><author><name sortKey="Saleheen, Danish" sort="Saleheen, Danish" uniqKey="Saleheen D" first="Danish" last="Saleheen">Danish Saleheen</name><affiliation><nlm:aff id="A28">Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A27">Centre for Non-Communicable Diseases, Karachi, Pakistan</nlm:aff></affiliation><affiliation><nlm:aff id="A1">Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Asselbergs, Folkert W" sort="Asselbergs, Folkert W" uniqKey="Asselbergs F" first="Folkert W" last="Asselbergs">Folkert W. Asselbergs</name><affiliation><nlm:aff id="A15">Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A101">Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A163">Faculty of Population Health Sciences, Institute of Cardiovascular Science, University College London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Lindgren, Cecilia M" sort="Lindgren, Cecilia M" uniqKey="Lindgren C" first="Cecilia M" last="Lindgren">Cecilia M. Lindgren</name><affiliation><nlm:aff id="A164">The Big Data Institute at the Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A9">Program in Medical and Population Genetics, Broad Institute, 7 Cambridge Center, Cambridge, Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A20">Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK</nlm:aff></affiliation></author><author><name sortKey="Danesh, John" sort="Danesh, John" uniqKey="Danesh J" first="John" last="Danesh">John Danesh</name><affiliation><nlm:aff id="A1">Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A165">Wellcome Trust Sanger Institute, Hinxton, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A54">The National Institute for Health Research Blood and Transplant Research Unit in Donor Health and Genomics, University of Cambridge, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Wain, Louise V" sort="Wain, Louise V" uniqKey="Wain L" first="Louise V" last="Wain">Louise V. Wain</name><affiliation><nlm:aff id="A6">Department of Health Sciences, University of Leicester, Leicester, UK</nlm:aff></affiliation></author><author><name sortKey="Butterworth, Adam S" sort="Butterworth, Adam S" uniqKey="Butterworth A" first="Adam S" last="Butterworth">Adam S. Butterworth</name><affiliation><nlm:aff id="A1">Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A166">The National Institute for Health Research Blood and Transplant Research</nlm:aff></affiliation></author><author><name sortKey="Howson, Joanna Mm" sort="Howson, Joanna Mm" uniqKey="Howson J" first="Joanna Mm" last="Howson">Joanna Mm Howson</name><affiliation><nlm:aff id="A1">Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Munroe, Patricia B" sort="Munroe, Patricia B" uniqKey="Munroe P" first="Patricia B" last="Munroe">Patricia B. Munroe</name><affiliation><nlm:aff id="A4">Clinical Pharmacology, William Harvey Research Institute, Queen Mary University of London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A5">National Institute for Health Research Barts Cardiovascular Biomedical Research Unit, Queen Mary University of London, London, UK</nlm:aff></affiliation></author></analytic><series><title level="j">Nature genetics</title><idno type="ISSN">1061-4036</idno><idno type="eISSN">1546-1718</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P2">High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to ~192,000 individuals, and used ~155,063 samples for independent replication. We identified 31 novel blood pressure or hypertension associated genetic regions in the general population, including three rare missense variants in <italic>RBM47</italic>, <italic>COL21A1</italic> and <italic>RRAS</italic> with larger effects (>1.5mmHg/allele) than common variants. Multiple rare, nonsense and missense variant associations were found in <italic>A2ML1</italic> and a low-frequency nonsense variant in <italic>ENPEP</italic> was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Lim, Ss" uniqKey="Lim S">SS Lim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rapsomaniki, E" uniqKey="Rapsomaniki E">E Rapsomaniki</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Munroe, Pb" uniqKey="Munroe P">PB Munroe</name></author><author><name sortKey="Barnes, Mr" uniqKey="Barnes M">MR Barnes</name></author><author><name sortKey="Caulfield, Mj" uniqKey="Caulfield M">MJ Caulfield</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ehret, Gb" uniqKey="Ehret G">GB Ehret</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wain, Lv" uniqKey="Wain L">LV Wain</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Johnson, T" uniqKey="Johnson T">T Johnson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tomaszewski, M" uniqKey="Tomaszewski M">M Tomaszewski</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tragante, V" uniqKey="Tragante V">V Tragante</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ganesh, Sk" uniqKey="Ganesh S">SK Ganesh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Simino, J" uniqKey="Simino J">J Simino</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhu, X" uniqKey="Zhu X">X Zhu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Salfati, E" uniqKey="Salfati E">E Salfati</name></author><author><name sortKey="Morrison, Ac" uniqKey="Morrison A">AC Morrison</name></author><author><name sortKey="Boerwinkle, E" uniqKey="Boerwinkle E">E Boerwinkle</name></author><author><name sortKey="Chakravarti, A" uniqKey="Chakravarti A">A Chakravarti</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Schork, Nj" uniqKey="Schork N">NJ Schork</name></author><author><name sortKey="Murray, Ss" uniqKey="Murray S">SS Murray</name></author><author><name sortKey="Frazer, Ka" uniqKey="Frazer K">KA Frazer</name></author><author><name sortKey="Topol, Ej" uniqKey="Topol E">EJ Topol</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nejentsev, S" uniqKey="Nejentsev S">S Nejentsev</name></author><author><name sortKey="Walker, N" uniqKey="Walker N">N Walker</name></author><author><name sortKey="Riches, D" uniqKey="Riches D">D Riches</name></author><author><name sortKey="Egholm, M" uniqKey="Egholm M">M Egholm</name></author><author><name sortKey="Todd, Ja" uniqKey="Todd J">JA Todd</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liu, Dj" uniqKey="Liu D">DJ Liu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wu, Mc" uniqKey="Wu M">MC Wu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, B" uniqKey="Li B">B Li</name></author><author><name sortKey="Leal, Sm" uniqKey="Leal S">SM Leal</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vissers, Le" uniqKey="Vissers L">LE Vissers</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Schunkert, H" uniqKey="Schunkert H">H Schunkert</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Arking, De" uniqKey="Arking D">DE Arking</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Den Hoed, M" uniqKey="Den Hoed M">M den Hoed</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Traylor, M" uniqKey="Traylor M">M Traylor</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Smith, Nl" uniqKey="Smith N">NL Smith</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vasan, Rs" uniqKey="Vasan R">RS Vasan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ehret, Gb" uniqKey="Ehret G">GB Ehret</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Russo, Sb" uniqKey="Russo S">SB Russo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Oudot Mellakh, T" uniqKey="Oudot Mellakh T">T Oudot-Mellakh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Smith, Nl" uniqKey="Smith N">NL Smith</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bleil, Me" uniqKey="Bleil M">ME Bleil</name></author><author><name sortKey="Gregorich, Se" uniqKey="Gregorich S">SE Gregorich</name></author><author><name sortKey="Mcconnell, D" uniqKey="Mcconnell D">D McConnell</name></author><author><name sortKey="Rosen, Mp" uniqKey="Rosen M">MP Rosen</name></author><author><name sortKey="Cedars, Mi" uniqKey="Cedars M">MI Cedars</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Guan, R" uniqKey="Guan R">R Guan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wozniak, Ma" uniqKey="Wozniak M">MA Wozniak</name></author><author><name sortKey="Kwong, L" uniqKey="Kwong L">L Kwong</name></author><author><name sortKey="Chodniewicz, D" uniqKey="Chodniewicz D">D Chodniewicz</name></author><author><name sortKey="Klemke, Rl" uniqKey="Klemke R">RL Klemke</name></author><author><name sortKey="Keely, Pj" uniqKey="Keely P">PJ Keely</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tuckwell, D" uniqKey="Tuckwell D">D Tuckwell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Huang, J" uniqKey="Huang J">J Huang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Segre, Av" uniqKey="Segre A">AV Segre</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Huan, T" uniqKey="Huan T">T Huan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Locke, Ae" uniqKey="Locke A">AE Locke</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wood, Ar" uniqKey="Wood A">AR Wood</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Park, Hw" uniqKey="Park H">HW Park</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sudlow, C" uniqKey="Sudlow C">C Sudlow</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Te Riet, L" uniqKey="Te Riet L">L Te Riet</name></author><author><name sortKey="Van Esch, Jh" uniqKey="Van Esch J">JH van Esch</name></author><author><name sortKey="Roks, Aj" uniqKey="Roks A">AJ Roks</name></author><author><name sortKey="Van Den Meiracker, Ah" uniqKey="Van Den Meiracker A">AH van den Meiracker</name></author><author><name sortKey="Danser, Ah" uniqKey="Danser A">AH Danser</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gao, J" uniqKey="Gao J">J Gao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tobin, Md" uniqKey="Tobin M">MD Tobin</name></author><author><name sortKey="Sheehan, Na" uniqKey="Sheehan N">NA Sheehan</name></author><author><name sortKey="Scurrah, Kj" uniqKey="Scurrah K">KJ Scurrah</name></author><author><name sortKey="Burton, Pr" uniqKey="Burton P">PR Burton</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mahajan, A" uniqKey="Mahajan A">A Mahajan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Willer, Cj" uniqKey="Willer C">CJ Willer</name></author><author><name sortKey="Li, Y" uniqKey="Li Y">Y Li</name></author><author><name sortKey="Abecasis, Gr" uniqKey="Abecasis G">GR Abecasis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Burgess, S" uniqKey="Burgess S">S Burgess</name></author><author><name sortKey="Thompson, Sg" uniqKey="Thompson S">SG Thompson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Thompson, Sg" uniqKey="Thompson S">SG Thompson</name></author><author><name sortKey="Sharp, Sj" uniqKey="Sharp S">SJ Sharp</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nica, Ac" uniqKey="Nica A">AC Nica</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Giambartolomei, C" uniqKey="Giambartolomei C">C Giambartolomei</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">9216904</journal-id><journal-id journal-id-type="pubmed-jr-id">2419</journal-id><journal-id journal-id-type="nlm-ta">Nat Genet</journal-id><journal-id journal-id-type="iso-abbrev">Nat. Genet.</journal-id><journal-title-group><journal-title>Nature genetics</journal-title></journal-title-group><issn pub-type="ppub">1061-4036</issn><issn pub-type="epub">1546-1718</issn></journal-meta><article-meta><article-id pub-id-type="pmid">27618447</article-id><article-id pub-id-type="pmc">5056636</article-id><article-id pub-id-type="doi">10.1038/ng.3654</article-id><article-id pub-id-type="manuscript">EMS69533</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension</article-title></title-group><contrib-group><contrib contrib-type="author" equal-contrib="yes"><name><surname>Surendran</surname><given-names>Praveen</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Drenos</surname><given-names>Fotios</given-names></name><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Young</surname><given-names>Robin</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Warren</surname><given-names>Helen</given-names></name><xref ref-type="aff" rid="A4">4</xref><xref ref-type="aff" rid="A5">5</xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Cook</surname><given-names>James P</given-names></name><xref ref-type="aff" rid="A6">6</xref><xref ref-type="aff" rid="A7">7</xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Manning</surname><given-names>Alisa K</given-names></name><xref ref-type="aff" rid="A8">8</xref><xref ref-type="aff" rid="A9">9</xref><xref ref-type="aff" rid="A10">10</xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Grarup</surname><given-names>Niels</given-names></name><xref ref-type="aff" rid="A11">11</xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Sim</surname><given-names>Xueling</given-names></name><xref ref-type="aff" rid="A12">12</xref><xref ref-type="aff" rid="A13">13</xref><xref ref-type="aff" rid="A14">14</xref></contrib><contrib contrib-type="author"><name><surname>Barnes</surname><given-names>Daniel R</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Witkowska</surname><given-names>Kate</given-names></name><xref ref-type="aff" rid="A4">4</xref><xref ref-type="aff" rid="A5">5</xref></contrib><contrib contrib-type="author"><name><surname>Staley</surname><given-names>James R</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Tragante</surname><given-names>Vinicius</given-names></name><xref ref-type="aff" rid="A15">15</xref></contrib><contrib contrib-type="author"><name><surname>Tukiainen</surname><given-names>Taru</given-names></name><xref ref-type="aff" rid="A8">8</xref><xref ref-type="aff" rid="A9">9</xref><xref ref-type="aff" rid="A16">16</xref></contrib><contrib contrib-type="author"><name><surname>Yaghootkar</surname><given-names>Hanieh</given-names></name><xref ref-type="aff" rid="A17">17</xref></contrib><contrib contrib-type="author"><name><surname>Masca</surname><given-names>Nicholas</given-names></name><xref ref-type="aff" rid="A18">18</xref><xref ref-type="aff" rid="A19">19</xref></contrib><contrib contrib-type="author"><name><surname>Freitag</surname><given-names>Daniel F</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Ferreira</surname><given-names>Teresa</given-names></name><xref ref-type="aff" rid="A20">20</xref></contrib><contrib contrib-type="author"><name><surname>Giannakopoulou</surname><given-names>Olga</given-names></name><xref ref-type="aff" rid="A21">21</xref></contrib><contrib contrib-type="author"><name><surname>Tinker</surname><given-names>Andrew</given-names></name><xref ref-type="aff" rid="A21">21</xref><xref ref-type="aff" rid="A5">5</xref></contrib><contrib contrib-type="author"><name><surname>Harakalova</surname><given-names>Magdalena</given-names></name><xref ref-type="aff" rid="A15">15</xref></contrib><contrib contrib-type="author"><name><surname>Mihailov</surname><given-names>Evelin</given-names></name><xref ref-type="aff" rid="A22">22</xref></contrib><contrib contrib-type="author"><name><surname>Liu</surname><given-names>Chunyu</given-names></name><xref ref-type="aff" rid="A23">23</xref></contrib><contrib contrib-type="author"><name><surname>Kraja</surname><given-names>Aldi T</given-names></name><xref ref-type="aff" rid="A24">24</xref><xref ref-type="aff" rid="A25">25</xref></contrib><contrib contrib-type="author"><name><surname>Fallgaard Nielsen</surname><given-names>Sune</given-names></name><xref ref-type="aff" rid="A26">26</xref></contrib><contrib contrib-type="author"><name><surname>Rasheed</surname><given-names>Asif</given-names></name><xref ref-type="aff" rid="A27">27</xref></contrib><contrib contrib-type="author"><name><surname>Samuel</surname><given-names>Maria</given-names></name><xref ref-type="aff" rid="A27">27</xref></contrib><contrib contrib-type="author"><name><surname>Zhao</surname><given-names>Wei</given-names></name><xref ref-type="aff" rid="A28">28</xref></contrib><contrib contrib-type="author"><name><surname>Bonnycastle</surname><given-names>Lori L</given-names></name><xref ref-type="aff" rid="A29">29</xref></contrib><contrib contrib-type="author"><name><surname>Jackson</surname><given-names>Anne U</given-names></name><xref ref-type="aff" rid="A13">13</xref><xref ref-type="aff" rid="A12">12</xref></contrib><contrib contrib-type="author"><name><surname>Narisu</surname><given-names>Narisu</given-names></name><xref ref-type="aff" rid="A29">29</xref></contrib><contrib contrib-type="author"><name><surname>Swift</surname><given-names>Amy J</given-names></name><xref ref-type="aff" rid="A29">29</xref></contrib><contrib contrib-type="author"><name><surname>Southam</surname><given-names>Lorraine</given-names></name><xref ref-type="aff" rid="A30">30</xref><xref ref-type="aff" rid="A20">20</xref></contrib><contrib contrib-type="author"><name><surname>Marten</surname><given-names>Jonathan</given-names></name><xref ref-type="aff" rid="A31">31</xref></contrib><contrib contrib-type="author"><name><surname>Huyghe</surname><given-names>Jeroen R</given-names></name><xref ref-type="aff" rid="A13">13</xref><xref ref-type="aff" rid="A12">12</xref></contrib><contrib contrib-type="author"><name><surname>Stančáková</surname><given-names>Alena</given-names></name><xref ref-type="aff" rid="A32">32</xref></contrib><contrib contrib-type="author"><name><surname>Fava</surname><given-names>Cristiano</given-names></name><xref ref-type="aff" rid="A33">33</xref><xref ref-type="aff" rid="A34">34</xref></contrib><contrib contrib-type="author"><name><surname>Ohlsson</surname><given-names>Therese</given-names></name><xref ref-type="aff" rid="A33">33</xref></contrib><contrib contrib-type="author"><name><surname>Matchan</surname><given-names>Angela</given-names></name><xref ref-type="aff" rid="A30">30</xref></contrib><contrib contrib-type="author"><name><surname>Stirrups</surname><given-names>Kathleen E</given-names></name><xref ref-type="aff" rid="A21">21</xref><xref ref-type="aff" rid="A35">35</xref></contrib><contrib contrib-type="author"><name><surname>Bork-Jensen</surname><given-names>Jette</given-names></name><xref ref-type="aff" rid="A11">11</xref></contrib><contrib contrib-type="author"><name><surname>Gjesing</surname><given-names>Anette P</given-names></name><xref ref-type="aff" rid="A11">11</xref></contrib><contrib contrib-type="author"><name><surname>Kontto</surname><given-names>Jukka</given-names></name><xref ref-type="aff" rid="A36">36</xref></contrib><contrib contrib-type="author"><name><surname>Perola</surname><given-names>Markus</given-names></name><xref ref-type="aff" rid="A36">36</xref><xref ref-type="aff" rid="A37">37</xref><xref ref-type="aff" rid="A22">22</xref></contrib><contrib contrib-type="author"><name><surname>Shaw-Hawkins</surname><given-names>Susan</given-names></name><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Havulinna</surname><given-names>Aki S</given-names></name><xref ref-type="aff" rid="A36">36</xref></contrib><contrib contrib-type="author"><name><surname>Zhang</surname><given-names>He</given-names></name><xref ref-type="aff" rid="A38">38</xref></contrib><contrib contrib-type="author"><name><surname>Donnelly</surname><given-names>Louise A</given-names></name><xref ref-type="aff" rid="A39">39</xref></contrib><contrib contrib-type="author"><name><surname>Groves</surname><given-names>Christopher J</given-names></name><xref ref-type="aff" rid="A40">40</xref></contrib><contrib contrib-type="author"><name><surname>Rayner</surname><given-names>N William</given-names></name><xref ref-type="aff" rid="A40">40</xref><xref ref-type="aff" rid="A20">20</xref><xref ref-type="aff" rid="A30">30</xref></contrib><contrib contrib-type="author"><name><surname>Neville</surname><given-names>Matt J</given-names></name><xref ref-type="aff" rid="A40">40</xref><xref ref-type="aff" rid="A41">41</xref></contrib><contrib contrib-type="author"><name><surname>Robertson</surname><given-names>Neil R</given-names></name><xref ref-type="aff" rid="A20">20</xref><xref ref-type="aff" rid="A40">40</xref></contrib><contrib contrib-type="author"><name><surname>Yiorkas</surname><given-names>Andrianos M</given-names></name><xref ref-type="aff" rid="A42">42</xref><xref ref-type="aff" rid="A43">43</xref></contrib><contrib contrib-type="author"><name><surname>Herzig</surname><given-names>Karl-Heinz</given-names></name><xref ref-type="aff" rid="A44">44</xref><xref ref-type="aff" rid="A45">45</xref></contrib><contrib contrib-type="author"><name><surname>Kajantie</surname><given-names>Eero</given-names></name><xref ref-type="aff" rid="A36">36</xref><xref ref-type="aff" rid="A46">46</xref><xref ref-type="aff" rid="A47">47</xref></contrib><contrib contrib-type="author"><name><surname>Zhang</surname><given-names>Weihua</given-names></name><xref ref-type="aff" rid="A48">48</xref><xref ref-type="aff" rid="A49">49</xref></contrib><contrib contrib-type="author"><name><surname>Willems</surname><given-names>Sara M</given-names></name><xref ref-type="aff" rid="A50">50</xref></contrib><contrib contrib-type="author"><name><surname>Lannfelt</surname><given-names>Lars</given-names></name><xref ref-type="aff" rid="A51">51</xref></contrib><contrib contrib-type="author"><name><surname>Malerba</surname><given-names>Giovanni</given-names></name><xref ref-type="aff" rid="A52">52</xref></contrib><contrib contrib-type="author"><name><surname>Soranzo</surname><given-names>Nicole</given-names></name><xref ref-type="aff" rid="A53">53</xref><xref ref-type="aff" rid="A35">35</xref><xref ref-type="aff" rid="A54">54</xref></contrib><contrib contrib-type="author"><name><surname>Trabetti</surname><given-names>Elisabetta</given-names></name><xref ref-type="aff" rid="A52">52</xref></contrib><contrib contrib-type="author"><name><surname>Verweij</surname><given-names>Niek</given-names></name><xref ref-type="aff" rid="A55">55</xref><xref ref-type="aff" rid="A9">9</xref><xref ref-type="aff" rid="A56">56</xref></contrib><contrib contrib-type="author"><name><surname>Evangelou</surname><given-names>Evangelos</given-names></name><xref ref-type="aff" rid="A48">48</xref><xref ref-type="aff" rid="A57">57</xref></contrib><contrib contrib-type="author"><name><surname>Moayyeri</surname><given-names>Alireza</given-names></name><xref ref-type="aff" rid="A48">48</xref><xref ref-type="aff" rid="A58">58</xref></contrib><contrib contrib-type="author"><name><surname>Vergnaud</surname><given-names>Anne-Claire</given-names></name><xref ref-type="aff" rid="A48">48</xref></contrib><contrib contrib-type="author"><name><surname>Nelson</surname><given-names>Christopher P</given-names></name><xref ref-type="aff" rid="A18">18</xref><xref ref-type="aff" rid="A19">19</xref></contrib><contrib contrib-type="author"><name><surname>Poveda</surname><given-names>Alaitz</given-names></name><xref ref-type="aff" rid="A59">59</xref><xref ref-type="aff" rid="A60">60</xref></contrib><contrib contrib-type="author"><name><surname>Varga</surname><given-names>Tibor V</given-names></name><xref ref-type="aff" rid="A59">59</xref></contrib><contrib contrib-type="author"><name><surname>Caslake</surname><given-names>Muriel</given-names></name><xref ref-type="aff" rid="A61">61</xref></contrib><contrib contrib-type="author"><name><surname>de Craen</surname><given-names>Anton JM</given-names></name><xref ref-type="aff" rid="A62">62</xref><xref ref-type="aff" rid="A63">63</xref></contrib><contrib contrib-type="author"><name><surname>Trompet</surname><given-names>Stella</given-names></name><xref ref-type="aff" rid="A62">62</xref><xref ref-type="aff" rid="A64">64</xref></contrib><contrib contrib-type="author"><name><surname>Luan</surname><given-names>Jian’an</given-names></name><xref ref-type="aff" rid="A50">50</xref></contrib><contrib contrib-type="author"><name><surname>Scott</surname><given-names>Robert A</given-names></name><xref ref-type="aff" rid="A50">50</xref></contrib><contrib contrib-type="author"><name><surname>Harris</surname><given-names>Sarah E</given-names></name><xref ref-type="aff" rid="A65">65</xref><xref ref-type="aff" rid="A66">66</xref></contrib><contrib contrib-type="author"><name><surname>Liewald</surname><given-names>David CM</given-names></name><xref ref-type="aff" rid="A65">65</xref><xref ref-type="aff" rid="A67">67</xref></contrib><contrib contrib-type="author"><name><surname>Marioni</surname><given-names>Riccardo</given-names></name><xref ref-type="aff" rid="A65">65</xref><xref ref-type="aff" rid="A66">66</xref><xref ref-type="aff" rid="A68">68</xref></contrib><contrib contrib-type="author"><name><surname>Menni</surname><given-names>Cristina</given-names></name><xref ref-type="aff" rid="A69">69</xref></contrib><contrib contrib-type="author"><name><surname>Farmaki</surname><given-names>Aliki-Eleni</given-names></name><xref ref-type="aff" rid="A70">70</xref></contrib><contrib contrib-type="author"><name><surname>Hallmans</surname><given-names>Göran</given-names></name><xref ref-type="aff" rid="A71">71</xref></contrib><contrib contrib-type="author"><name><surname>Renström</surname><given-names>Frida</given-names></name><xref ref-type="aff" rid="A59">59</xref><xref ref-type="aff" rid="A71">71</xref></contrib><contrib contrib-type="author"><name><surname>Huffman</surname><given-names>Jennifer E</given-names></name><xref ref-type="aff" rid="A31">31</xref><xref ref-type="aff" rid="A23">23</xref></contrib><contrib contrib-type="author"><name><surname>Hassinen</surname><given-names>Maija</given-names></name><xref ref-type="aff" rid="A72">72</xref></contrib><contrib contrib-type="author"><name><surname>Burgess</surname><given-names>Stephen</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Vasan</surname><given-names>Ramachandran S</given-names></name><xref ref-type="aff" rid="A23">23</xref><xref ref-type="aff" rid="A73">73</xref><xref ref-type="aff" rid="A74">74</xref></contrib><contrib contrib-type="author"><name><surname>Felix</surname><given-names>Janine F</given-names></name><xref ref-type="aff" rid="A75">75</xref></contrib><contrib contrib-type="author"><collab>CHARGE-Heart Failure Consortium</collab><xref ref-type="aff" rid="A76">76</xref></contrib><contrib contrib-type="author"><name><surname>Uria-Nickelsen</surname><given-names>Maria</given-names></name><xref ref-type="aff" rid="A77">77</xref></contrib><contrib contrib-type="author"><name><surname>Malarstig</surname><given-names>Anders</given-names></name><xref ref-type="aff" rid="A78">78</xref></contrib><contrib contrib-type="author"><name><surname>Reily</surname><given-names>Dermot F</given-names></name><xref ref-type="aff" rid="A79">79</xref></contrib><contrib contrib-type="author"><name><surname>Hoek</surname><given-names>Maarten</given-names></name><xref ref-type="aff" rid="A80">80</xref></contrib><contrib contrib-type="author"><name><surname>Vogt</surname><given-names>Thomas</given-names></name><xref ref-type="aff" rid="A80">80</xref><xref ref-type="aff" rid="A81">81</xref></contrib><contrib contrib-type="author"><name><surname>Lin</surname><given-names>Honghuang</given-names></name><xref ref-type="aff" rid="A23">23</xref><xref ref-type="aff" rid="A82">82</xref></contrib><contrib contrib-type="author"><name><surname>Lieb</surname><given-names>Wolfgang</given-names></name><xref ref-type="aff" rid="A83">83</xref></contrib><contrib contrib-type="author"><collab>EchoGen Consortium</collab><xref ref-type="aff" rid="A76">76</xref></contrib><contrib contrib-type="author"><name><surname>Traylor</surname><given-names>Matthew</given-names></name><xref ref-type="aff" rid="A84">84</xref></contrib><contrib contrib-type="author"><name><surname>Markus</surname><given-names>Hugh F</given-names></name><xref ref-type="aff" rid="A84">84</xref></contrib><contrib contrib-type="author"><collab>METASTROKE Consortium</collab><xref ref-type="aff" rid="A76">76</xref></contrib><contrib contrib-type="author"><name><surname>Highland</surname><given-names>Heather M</given-names></name><xref ref-type="aff" rid="A85">85</xref></contrib><contrib contrib-type="author"><name><surname>Justice</surname><given-names>Anne E</given-names></name><xref ref-type="aff" rid="A85">85</xref></contrib><contrib contrib-type="author"><name><surname>Marouli</surname><given-names>Eirini</given-names></name><xref ref-type="aff" rid="A21">21</xref></contrib><contrib contrib-type="author"><collab>GIANT Consortium</collab><xref ref-type="aff" rid="A76">76</xref></contrib><contrib contrib-type="author"><name><surname>Lindström</surname><given-names>Jaana</given-names></name><xref ref-type="aff" rid="A36">36</xref></contrib><contrib contrib-type="author"><name><surname>Uusitupa</surname><given-names>Matti</given-names></name><xref ref-type="aff" rid="A86">86</xref><xref ref-type="aff" rid="A87">87</xref></contrib><contrib contrib-type="author"><name><surname>Komulainen</surname><given-names>Pirjo</given-names></name><xref ref-type="aff" rid="A72">72</xref></contrib><contrib contrib-type="author"><name><surname>Lakka</surname><given-names>Timo A</given-names></name><xref ref-type="aff" rid="A72">72</xref><xref ref-type="aff" rid="A88">88</xref><xref ref-type="aff" rid="A89">89</xref></contrib><contrib contrib-type="author"><name><surname>Rauramaa</surname><given-names>Rainer</given-names></name><xref ref-type="aff" rid="A72">72</xref><xref ref-type="aff" rid="A89">89</xref></contrib><contrib contrib-type="author"><name><surname>Polasek</surname><given-names>Ozren</given-names></name><xref ref-type="aff" rid="A90">90</xref><xref ref-type="aff" rid="A91">91</xref></contrib><contrib contrib-type="author"><name><surname>Rudan</surname><given-names>Igor</given-names></name><xref ref-type="aff" rid="A90">90</xref></contrib><contrib contrib-type="author"><name><surname>Rolandsson</surname><given-names>Olov</given-names></name><xref ref-type="aff" rid="A92">92</xref></contrib><contrib contrib-type="author"><name><surname>Franks</surname><given-names>Paul W</given-names></name><xref ref-type="aff" rid="A59">59</xref><xref ref-type="aff" rid="A92">92</xref><xref ref-type="aff" rid="A93">93</xref></contrib><contrib contrib-type="author"><name><surname>Dedoussis</surname><given-names>George</given-names></name><xref ref-type="aff" rid="A70">70</xref></contrib><contrib contrib-type="author"><name><surname>Spector</surname><given-names>Timothy D</given-names></name><xref ref-type="aff" rid="A69">69</xref></contrib><contrib contrib-type="author"><collab>EPIC-InterAct Consortium</collab><xref ref-type="aff" rid="A76">76</xref></contrib><contrib contrib-type="author"><name><surname>Jousilahti</surname><given-names>Pekka</given-names></name><xref ref-type="aff" rid="A36">36</xref></contrib><contrib contrib-type="author"><name><surname>Männistö</surname><given-names>Satu</given-names></name><xref ref-type="aff" rid="A36">36</xref></contrib><contrib contrib-type="author"><name><surname>Deary</surname><given-names>Ian J</given-names></name><xref ref-type="aff" rid="A65">65</xref><xref ref-type="aff" rid="A67">67</xref></contrib><contrib contrib-type="author"><name><surname>Starr</surname><given-names>John M</given-names></name><xref ref-type="aff" rid="A65">65</xref><xref ref-type="aff" rid="A94">94</xref></contrib><contrib contrib-type="author"><name><surname>Langenberg</surname><given-names>Claudia</given-names></name><xref ref-type="aff" rid="A50">50</xref></contrib><contrib contrib-type="author"><name><surname>Wareham</surname><given-names>Nick J</given-names></name><xref ref-type="aff" rid="A50">50</xref></contrib><contrib contrib-type="author"><name><surname>Brown</surname><given-names>Morris J</given-names></name><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Dominiczak</surname><given-names>Anna F</given-names></name><xref ref-type="aff" rid="A95">95</xref></contrib><contrib contrib-type="author"><name><surname>Connell</surname><given-names>John M</given-names></name><xref ref-type="aff" rid="A39">39</xref></contrib><contrib contrib-type="author"><name><surname>Jukema</surname><given-names>J Wouter</given-names></name><xref ref-type="aff" rid="A64">64</xref><xref ref-type="aff" rid="A96">96</xref></contrib><contrib contrib-type="author"><name><surname>Sattar</surname><given-names>Naveed</given-names></name><xref ref-type="aff" rid="A95">95</xref></contrib><contrib contrib-type="author"><name><surname>Ford</surname><given-names>Ian</given-names></name><xref ref-type="aff" rid="A61">61</xref></contrib><contrib contrib-type="author"><name><surname>Packard</surname><given-names>Chris J</given-names></name><xref ref-type="aff" rid="A61">61</xref></contrib><contrib contrib-type="author"><name><surname>Esko</surname><given-names>Tõnu</given-names></name><xref ref-type="aff" rid="A22">22</xref><xref ref-type="aff" rid="A97">97</xref><xref ref-type="aff" rid="A8">8</xref><xref ref-type="aff" rid="A9">9</xref></contrib><contrib contrib-type="author"><name><surname>Mägi</surname><given-names>Reedik</given-names></name><xref ref-type="aff" rid="A22">22</xref></contrib><contrib contrib-type="author"><name><surname>Metspalu</surname><given-names>Andres</given-names></name><xref ref-type="aff" rid="A22">22</xref><xref ref-type="aff" rid="A98">98</xref></contrib><contrib contrib-type="author"><name><surname>de Boer</surname><given-names>Rudolf A</given-names></name><xref ref-type="aff" rid="A99">99</xref></contrib><contrib contrib-type="author"><name><surname>van der Meer</surname><given-names>Peter</given-names></name><xref ref-type="aff" rid="A99">99</xref></contrib><contrib contrib-type="author"><name><surname>van der Harst</surname><given-names>Pim</given-names></name><xref ref-type="aff" rid="A99">99</xref><xref ref-type="aff" rid="A100">100</xref><xref ref-type="aff" rid="A101">101</xref></contrib><contrib contrib-type="author"><collab>Lifelines Cohort Study</collab><xref ref-type="aff" rid="A76">76</xref></contrib><contrib contrib-type="author"><name><surname>Gambaro</surname><given-names>Giovanni</given-names></name><xref ref-type="aff" rid="A102">102</xref></contrib><contrib contrib-type="author"><name><surname>Ingelsson</surname><given-names>Erik</given-names></name><xref ref-type="aff" rid="A103">103</xref><xref ref-type="aff" rid="A104">104</xref></contrib><contrib contrib-type="author"><name><surname>Lind</surname><given-names>Lars</given-names></name><xref ref-type="aff" rid="A103">103</xref></contrib><contrib contrib-type="author"><name><surname>de Bakker</surname><given-names>Paul IW</given-names></name><xref ref-type="aff" rid="A105">105</xref><xref ref-type="aff" rid="A106">106</xref></contrib><contrib contrib-type="author"><name><surname>Numans</surname><given-names>Mattijs E</given-names></name><xref ref-type="aff" rid="A107">107</xref><xref ref-type="aff" rid="A106">106</xref></contrib><contrib contrib-type="author"><name><surname>Brandslund</surname><given-names>Ivan</given-names></name><xref ref-type="aff" rid="A108">108</xref><xref ref-type="aff" rid="A109">109</xref></contrib><contrib contrib-type="author"><name><surname>Christensen</surname><given-names>Cramer</given-names></name><xref ref-type="aff" rid="A110">110</xref></contrib><contrib contrib-type="author"><name><surname>Petersen</surname><given-names>Eva RB</given-names></name><xref ref-type="aff" rid="A111">111</xref></contrib><contrib contrib-type="author"><name><surname>Korpi-Hyövälti</surname><given-names>Eeva</given-names></name><xref ref-type="aff" rid="A112">112</xref></contrib><contrib contrib-type="author"><name><surname>Oksa</surname><given-names>Heikki</given-names></name><xref ref-type="aff" rid="A113">113</xref></contrib><contrib contrib-type="author"><name><surname>Chambers</surname><given-names>John C</given-names></name><xref ref-type="aff" rid="A48">48</xref><xref ref-type="aff" rid="A49">49</xref><xref ref-type="aff" rid="A114">114</xref></contrib><contrib contrib-type="author"><name><surname>Kooner</surname><given-names>Jaspal S</given-names></name><xref ref-type="aff" rid="A49">49</xref><xref ref-type="aff" rid="A115">115</xref><xref ref-type="aff" rid="A114">114</xref></contrib><contrib contrib-type="author"><name><surname>Blakemore</surname><given-names>Alexandra IF</given-names></name><xref ref-type="aff" rid="A42">42</xref><xref ref-type="aff" rid="A43">43</xref></contrib><contrib contrib-type="author"><name><surname>Franks</surname><given-names>Steve</given-names></name><xref ref-type="aff" rid="A116">116</xref></contrib><contrib contrib-type="author"><name><surname>Jarvelin</surname><given-names>Marjo-Riitta</given-names></name><xref ref-type="aff" rid="A117">117</xref><xref ref-type="aff" rid="A118">118</xref><xref ref-type="aff" rid="A119">119</xref><xref ref-type="aff" rid="A120">120</xref></contrib><contrib contrib-type="author"><name><surname>Husemoen</surname><given-names>Lise L</given-names></name><xref ref-type="aff" rid="A121">121</xref></contrib><contrib contrib-type="author"><name><surname>Linneberg</surname><given-names>Allan</given-names></name><xref ref-type="aff" rid="A121">121</xref><xref ref-type="aff" rid="A122">122</xref><xref ref-type="aff" rid="A123">123</xref></contrib><contrib contrib-type="author"><name><surname>Skaaby</surname><given-names>Tea</given-names></name><xref ref-type="aff" rid="A121">121</xref></contrib><contrib contrib-type="author"><name><surname>Thuesen</surname><given-names>Betina</given-names></name><xref ref-type="aff" rid="A121">121</xref></contrib><contrib contrib-type="author"><name><surname>Karpe</surname><given-names>Fredrik</given-names></name><xref ref-type="aff" rid="A40">40</xref><xref ref-type="aff" rid="A41">41</xref></contrib><contrib contrib-type="author"><name><surname>Tuomilehto</surname><given-names>Jaakko</given-names></name><xref ref-type="aff" rid="A36">36</xref><xref ref-type="aff" rid="A124">124</xref><xref ref-type="aff" rid="A125">125</xref><xref ref-type="aff" rid="A126">126</xref></contrib><contrib contrib-type="author"><name><surname>Doney</surname><given-names>Alex SF</given-names></name><xref ref-type="aff" rid="A39">39</xref></contrib><contrib contrib-type="author"><name><surname>Morris</surname><given-names>Andrew D</given-names></name><xref ref-type="aff" rid="A127">127</xref></contrib><contrib contrib-type="author"><name><surname>Palmer</surname><given-names>Colin NA</given-names></name><xref ref-type="aff" rid="A39">39</xref></contrib><contrib contrib-type="author"><name><surname>Holmen</surname><given-names>Oddgeir Lingaas</given-names></name><xref ref-type="aff" rid="A128">128</xref><xref ref-type="aff" rid="A129">129</xref></contrib><contrib contrib-type="author"><name><surname>Hveem</surname><given-names>Kristian</given-names></name><xref ref-type="aff" rid="A128">128</xref><xref ref-type="aff" rid="A130">130</xref></contrib><contrib contrib-type="author"><name><surname>Willer</surname><given-names>Cristen J</given-names></name><xref ref-type="aff" rid="A38">38</xref><xref ref-type="aff" rid="A131">131</xref><xref ref-type="aff" rid="A132">132</xref></contrib><contrib contrib-type="author"><name><surname>Tuomi</surname><given-names>Tiinamaija</given-names></name><xref ref-type="aff" rid="A133">133</xref><xref ref-type="aff" rid="A134">134</xref></contrib><contrib contrib-type="author"><name><surname>Groop</surname><given-names>Leif</given-names></name><xref ref-type="aff" rid="A135">135</xref><xref ref-type="aff" rid="A134">134</xref></contrib><contrib contrib-type="author"><name><surname>Käräjämäki</surname><given-names>AnneMari</given-names></name><xref ref-type="aff" rid="A136">136</xref><xref ref-type="aff" rid="A137">137</xref></contrib><contrib contrib-type="author"><name><surname>Palotie</surname><given-names>Aarno</given-names></name><xref ref-type="aff" rid="A16">16</xref><xref ref-type="aff" rid="A9">9</xref><xref ref-type="aff" rid="A134">134</xref><xref ref-type="aff" rid="A138">138</xref></contrib><contrib contrib-type="author"><name><surname>Ripatti</surname><given-names>Samuli</given-names></name><xref ref-type="aff" rid="A134">134</xref><xref ref-type="aff" rid="A139">139</xref><xref ref-type="aff" rid="A30">30</xref></contrib><contrib contrib-type="author"><name><surname>Salomaa</surname><given-names>Veikko</given-names></name><xref ref-type="aff" rid="A36">36</xref></contrib><contrib contrib-type="author"><name><surname>Alam</surname><given-names>Dewan S</given-names></name><xref ref-type="aff" rid="A140">140</xref></contrib><contrib contrib-type="author"><name><surname>Shafi Majumder</surname><given-names>Abdulla al</given-names></name><xref ref-type="aff" rid="A141">141</xref></contrib><contrib contrib-type="author"><name><surname>Di Angelantonio</surname><given-names>Emanuele</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A54">54</xref></contrib><contrib contrib-type="author"><name><surname>Chowdhury</surname><given-names>Rajiv</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>McCarthy</surname><given-names>Mark I</given-names></name><xref ref-type="aff" rid="A40">40</xref><xref ref-type="aff" rid="A41">41</xref><xref ref-type="aff" rid="A20">20</xref></contrib><contrib contrib-type="author"><name><surname>Poulter</surname><given-names>Neil</given-names></name><xref ref-type="aff" rid="A142">142</xref></contrib><contrib contrib-type="author"><name><surname>Stanton</surname><given-names>Alice V</given-names></name><xref ref-type="aff" rid="A143">143</xref></contrib><contrib contrib-type="author"><name><surname>Sever</surname><given-names>Peter</given-names></name><xref ref-type="aff" rid="A142">142</xref></contrib><contrib contrib-type="author"><name><surname>Amouyel</surname><given-names>Philippe</given-names></name><xref ref-type="aff" rid="A144">144</xref><xref ref-type="aff" rid="A145">145</xref><xref ref-type="aff" rid="A146">146</xref><xref ref-type="aff" rid="A147">147</xref></contrib><contrib contrib-type="author"><name><surname>Arveiler</surname><given-names>Dominique</given-names></name><xref ref-type="aff" rid="A148">148</xref></contrib><contrib contrib-type="author"><name><surname>Blankenberg</surname><given-names>Stefan</given-names></name><xref ref-type="aff" rid="A149">149</xref><xref ref-type="aff" rid="A150">150</xref></contrib><contrib contrib-type="author"><name><surname>Ferrières</surname><given-names>Jean</given-names></name><xref ref-type="aff" rid="A151">151</xref></contrib><contrib contrib-type="author"><name><surname>Kee</surname><given-names>Frank</given-names></name><xref ref-type="aff" rid="A152">152</xref></contrib><contrib contrib-type="author"><name><surname>Kuulasmaa</surname><given-names>Kari</given-names></name><xref ref-type="aff" rid="A36">36</xref></contrib><contrib contrib-type="author"><name><surname>Müller-Nurasyid</surname><given-names>Martina</given-names></name><xref ref-type="aff" rid="A153">153</xref><xref ref-type="aff" rid="A154">154</xref><xref ref-type="aff" rid="A155">155</xref></contrib><contrib contrib-type="author"><name><surname>Veronesi</surname><given-names>Giovanni</given-names></name><xref ref-type="aff" rid="A156">156</xref></contrib><contrib contrib-type="author"><name><surname>Virtamo</surname><given-names>Jarmo</given-names></name><xref ref-type="aff" rid="A36">36</xref></contrib><contrib contrib-type="author"><name><surname>Deloukas</surname><given-names>Panos</given-names></name><xref ref-type="aff" rid="A21">21</xref><xref ref-type="aff" rid="A157">157</xref></contrib><contrib contrib-type="author"><collab>Wellcome Trust Case Control Consortium</collab><xref ref-type="aff" rid="A76">76</xref></contrib><contrib contrib-type="author"><name><surname>Elliott</surname><given-names>Paul</given-names></name><xref ref-type="aff" rid="A117">117</xref></contrib><contrib contrib-type="author"><collab>Understanding Society Scientific Group</collab><xref ref-type="aff" rid="A76">76</xref></contrib><contrib contrib-type="author"><name><surname>Zeggini</surname><given-names>Eleftheria</given-names></name><xref ref-type="aff" rid="A30">30</xref></contrib><contrib contrib-type="author"><name><surname>Kathiresan</surname><given-names>Sekar</given-names></name><xref ref-type="aff" rid="A56">56</xref><xref ref-type="aff" rid="A158">158</xref><xref ref-type="aff" rid="A159">159</xref><xref ref-type="aff" rid="A9">9</xref></contrib><contrib contrib-type="author"><name><surname>Melander</surname><given-names>Olle</given-names></name><xref ref-type="aff" rid="A33">33</xref></contrib><contrib contrib-type="author"><name><surname>Kuusisto</surname><given-names>Johanna</given-names></name><xref ref-type="aff" rid="A32">32</xref></contrib><contrib contrib-type="author"><name><surname>Laakso</surname><given-names>Markku</given-names></name><xref ref-type="aff" rid="A32">32</xref></contrib><contrib contrib-type="author"><name><surname>Padmanabhan</surname><given-names>Sandosh</given-names></name><xref ref-type="aff" rid="A95">95</xref></contrib><contrib contrib-type="author"><name><surname>Porteous</surname><given-names>David</given-names></name><xref ref-type="aff" rid="A66">66</xref></contrib><contrib contrib-type="author"><name><surname>Hayward</surname><given-names>Caroline</given-names></name><xref ref-type="aff" rid="A31">31</xref></contrib><contrib contrib-type="author"><name><surname>Scotland</surname><given-names>Generation</given-names></name><xref ref-type="aff" rid="A160">160</xref></contrib><contrib contrib-type="author"><name><surname>Collins</surname><given-names>Francis S</given-names></name><xref ref-type="aff" rid="A29">29</xref></contrib><contrib contrib-type="author"><name><surname>Mohlke</surname><given-names>Karen L</given-names></name><xref ref-type="aff" rid="A161">161</xref></contrib><contrib contrib-type="author"><name><surname>Hansen</surname><given-names>Torben</given-names></name><xref ref-type="aff" rid="A11">11</xref></contrib><contrib contrib-type="author"><name><surname>Pedersen</surname><given-names>Oluf</given-names></name><xref ref-type="aff" rid="A11">11</xref></contrib><contrib contrib-type="author"><name><surname>Boehnke</surname><given-names>Michael</given-names></name><xref ref-type="aff" rid="A13">13</xref><xref ref-type="aff" rid="A12">12</xref></contrib><contrib contrib-type="author"><name><surname>Stringham</surname><given-names>Heather M</given-names></name><xref ref-type="aff" rid="A13">13</xref><xref ref-type="aff" rid="A12">12</xref></contrib><contrib contrib-type="author"><collab>EPIC-CVD Consortium</collab><xref ref-type="aff" rid="A76">76</xref></contrib><contrib contrib-type="author"><name><surname>Frossard</surname><given-names>Philippe</given-names></name><xref ref-type="aff" rid="A27">27</xref></contrib><contrib contrib-type="author"><name><surname>Newton-Cheh</surname><given-names>Christopher</given-names></name><xref ref-type="aff" rid="A56">56</xref><xref ref-type="aff" rid="A158">158</xref></contrib><contrib contrib-type="author"><collab>CHARGE+ Exome Chip Blood Pressure Consortium</collab><xref ref-type="aff" rid="A76">76</xref></contrib><contrib contrib-type="author"><name><surname>Tobin</surname><given-names>Martin D</given-names></name><xref ref-type="aff" rid="A6">6</xref></contrib><contrib contrib-type="author"><name><surname>Nordestgaard</surname><given-names>Børge Grønne</given-names></name><xref ref-type="aff" rid="A26">26</xref></contrib><contrib contrib-type="author"><collab>T2D-GENES Consortium</collab><xref ref-type="aff" rid="A76">76</xref></contrib><contrib contrib-type="author"><collab>GoT2DGenes Consortium</collab><xref ref-type="aff" rid="A76">76</xref></contrib><contrib contrib-type="author"><collab>ExomeBP Consortium</collab><xref ref-type="aff" rid="A76">76</xref></contrib><contrib contrib-type="author"><collab>CHD Exome+ Consortium</collab><xref ref-type="aff" rid="A76">76</xref></contrib><contrib contrib-type="author"><name><surname>Caulfield</surname><given-names>Mark J</given-names></name><xref ref-type="aff" rid="A4">4</xref><xref ref-type="aff" rid="A5">5</xref></contrib><contrib contrib-type="author"><name><surname>Mahajan</surname><given-names>Anubha</given-names></name><xref ref-type="aff" rid="A20">20</xref></contrib><contrib contrib-type="author"><name><surname>Morris</surname><given-names>Andrew P</given-names></name><xref ref-type="aff" rid="A20">20</xref><xref ref-type="aff" rid="A7">7</xref></contrib><contrib contrib-type="author"><name><surname>Tomaszewski</surname><given-names>Maciej</given-names></name><xref ref-type="aff" rid="A18">18</xref><xref ref-type="aff" rid="A19">19</xref><xref ref-type="aff" rid="A162">162</xref></contrib><contrib contrib-type="author"><name><surname>Samani</surname><given-names>Nilesh J</given-names></name><xref ref-type="aff" rid="A18">18</xref><xref ref-type="aff" rid="A19">19</xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Saleheen</surname><given-names>Danish</given-names></name><xref ref-type="aff" rid="A28">28</xref><xref ref-type="aff" rid="A27">27</xref><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Asselbergs</surname><given-names>Folkert W</given-names></name><xref ref-type="aff" rid="A15">15</xref><xref ref-type="aff" rid="A101">101</xref><xref ref-type="aff" rid="A163">163</xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Lindgren</surname><given-names>Cecilia M</given-names></name><xref ref-type="aff" rid="A164">164</xref><xref ref-type="aff" rid="A9">9</xref><xref ref-type="aff" rid="A20">20</xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Danesh</surname><given-names>John</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A165">165</xref><xref ref-type="aff" rid="A54">54</xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Wain</surname><given-names>Louise V</given-names></name><xref ref-type="aff" rid="A6">6</xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Butterworth</surname><given-names>Adam S</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A166">166</xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Howson</surname><given-names>Joanna MM</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="author-notes" rid="FN1">168</xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Munroe</surname><given-names>Patricia B</given-names></name><xref ref-type="aff" rid="A4">4</xref><xref ref-type="aff" rid="A5">5</xref><xref ref-type="author-notes" rid="FN1">168</xref></contrib></contrib-group><aff id="A1"><label>1</label>Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK</aff><aff id="A2"><label>2</label>Medical Research Council Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol, UK</aff><aff id="A3"><label>3</label>Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, Rayne Building University College London, London, UK</aff><aff id="A4"><label>4</label>Clinical Pharmacology, William Harvey Research Institute, Queen Mary University of London, London, UK</aff><aff id="A5"><label>5</label>National Institute for Health Research Barts Cardiovascular Biomedical Research Unit, Queen Mary University of London, London, UK</aff><aff id="A6"><label>6</label>Department of Health Sciences, University of Leicester, Leicester, UK</aff><aff id="A7"><label>7</label>Department of Biostatistics, University of Liverpool, Liverpool, UK</aff><aff id="A8"><label>8</label>Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA</aff><aff id="A9"><label>9</label>Program in Medical and Population Genetics, Broad Institute, 7 Cambridge Center, Cambridge, Massachusetts, USA</aff><aff id="A10"><label>10</label>Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, USA</aff><aff id="A11"><label>11</label>The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark</aff><aff id="A12"><label>12</label>Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA</aff><aff id="A13"><label>13</label>Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA</aff><aff id="A14"><label>14</label>Saw Swee Hock School of Public Health, National University of Singapore, National University Health System, Singapore</aff><aff id="A15"><label>15</label>Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands</aff><aff id="A16"><label>16</label>Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA</aff><aff id="A17"><label>17</label>Genetics of Complex Traits, Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK</aff><aff id="A18"><label>18</label>Department of Cardiovascular Sciences, University of Leicester, Leicester, UK</aff><aff id="A19"><label>19</label>National Institute for Health Research Leicester Biomedical Research Unit in Cardiovascular Disease, Leicester, UK</aff><aff id="A20"><label>20</label>Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK</aff><aff id="A21"><label>21</label>Heart Centre, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK</aff><aff id="A22"><label>22</label>Estonian Genome Center, University of Tartu, Tartu, Estonia</aff><aff id="A23"><label>23</label>National Heart, Lung, and Blood Institute’s and Boston University’s Framingham Heart Study, Framingham, Massachusetts, USA</aff><aff id="A24"><label>24</label>Division of Statistical Genomics, Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, Missouri, USA</aff><aff id="A25"><label>25</label>Department of Genetics, Washington University School of Medicine, St. Louis, Missouri, USA</aff><aff id="A26"><label>26</label>Department of Clinical Biochemistry Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark</aff><aff id="A27"><label>27</label>Centre for Non-Communicable Diseases, Karachi, Pakistan</aff><aff id="A28"><label>28</label>Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA</aff><aff id="A29"><label>29</label>Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA</aff><aff id="A30"><label>30</label>Wellcome Trust Sanger Institute, Genome Campus, Hinxton, UK</aff><aff id="A31"><label>31</label>Medical Research Council Human Genetics Unit, Medical Research Council Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK</aff><aff id="A32"><label>32</label>Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland</aff><aff id="A33"><label>33</label>University of Lund, Department of Clinical Sciences, Malmö, Sweden</aff><aff id="A34"><label>34</label>University of Verona, Department of Medicine, Verona, Italy</aff><aff id="A35"><label>35</label>Department of Haematology, University of Cambridge, Cambridge, UK</aff><aff id="A36"><label>36</label>Department of Health, National Institute for Health and Welfare, Helsinki, Finland</aff><aff id="A37"><label>37</label>Institute of Molecular Medicine FIMM, University of Helsinki, Finland</aff><aff id="A38"><label>38</label>Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan, USA</aff><aff id="A39"><label>39</label>Medical Research Institute, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK</aff><aff id="A40"><label>40</label>Oxford Centre for Diabetes, Endocrinology, and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK</aff><aff id="A41"><label>41</label>National Institute for Health Research Oxford Biomedical Research Centre, Oxford University Hospital Trusts, Oxford, UK</aff><aff id="A42"><label>42</label>Section of Investigative Medicine, Imperial College London, London, UK</aff><aff id="A43"><label>43</label>Department of Life Sciences, Brunel University London, London, UK</aff><aff id="A44"><label>44</label>Institute of Biomedicine, Biocenter Oulu, University of Oulu, Oulu, Finland</aff><aff id="A45"><label>45</label>Department of Gastroenterology and Metabolism, Poznan University of Medical Sciences, Poznan, Poland</aff><aff id="A46"><label>46</label>Hospital for Children and Adolescents, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland</aff><aff id="A47"><label>47</label>Department of Obstetrics and Gynaecology, Oulu University Hospital and University of Oulu, Oulu, Finland</aff><aff id="A48"><label>48</label>Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK</aff><aff id="A49"><label>49</label>Department of Cardiology, Ealing Hospital, Middlesex, UK</aff><aff id="A50"><label>50</label>Medical Research Council Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK</aff><aff id="A51"><label>51</label>Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden</aff><aff id="A52"><label>52</label>Section of Biology and Genetics, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy</aff><aff id="A53"><label>53</label>Human Genetics, Wellcome Trust Sanger Institute, Hinxton, UK</aff><aff id="A54"><label>54</label>The National Institute for Health Research Blood and Transplant Research Unit in Donor Health and Genomics, University of Cambridge, Cambridge, UK</aff><aff id="A55"><label>55</label>University Medical Center Groningen, University of Groningen, Department of Cardiology, The Netherlands</aff><aff id="A56"><label>56</label>Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA</aff><aff id="A57"><label>57</label>Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece</aff><aff id="A58"><label>58</label>Farr Institute of Health Informatics Research, Institute of Health Informatics, University College London, London, UK</aff><aff id="A59"><label>59</label>Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, Sweden</aff><aff id="A60"><label>60</label>Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Bilbao, Spain</aff><aff id="A61"><label>61</label>University of Glasgow, Glasgow, UK</aff><aff id="A62"><label>62</label>Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands</aff><aff id="A63"><label>63</label>Mr. De Craen suddenly passed away January 2016</aff><aff id="A64"><label>64</label>Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands</aff><aff id="A65"><label>65</label>Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK</aff><aff id="A66"><label>66</label>Centre for Genomic and Experimental Medicine, Medical Research Council Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK</aff><aff id="A67"><label>67</label>Department of Psychology, University of Edinburgh, Edinburgh, UK</aff><aff id="A68"><label>68</label>Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia</aff><aff id="A69"><label>69</label>Department of Twin Research and Genetic Epidemiology, King’s College London, UK</aff><aff id="A70"><label>70</label>Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece</aff><aff id="A71"><label>71</label>Department of Biobank Research, Umeå University, Umeå, Sweden</aff><aff id="A72"><label>72</label>Kuopio Research Institute of Exercise Medicine, Kuopio, Finland</aff><aff id="A73"><label>73</label>Section of Cardiology, Department of Medicine, Boston University Schools of Medicine and Public Health, Boston, Massachusetts, USA</aff><aff id="A74"><label>74</label>Sections of Preventive Medicine and Epidemiology, Department of Medicine, Boston University Schools of Medicine and Public Health, Boston, Massachusetts, USA</aff><aff id="A75"><label>75</label>Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands</aff><aff id="A76"><label>76</label>A full list of members and affiliations appears in the<xref ref-type="supplementary-material" rid="SD2">Supplementary Note</xref></aff><aff id="A77"><label>77</label>Development Management and Planning, Pfizer Worldwide Research and Development</aff><aff id="A78"><label>78</label>Pfizer Worldwide Research and Development, Stockholm, Sweden</aff><aff id="A79"><label>79</label>Merck Research Laboratories, Genetics and Pharmacogenomics, Boston, Massachusetts, USA</aff><aff id="A80"><label>80</label>Merck Research Laboratories, Cardiometabolic Disease, Kenilworth, New Jersey, USA</aff><aff id="A81"><label>81</label>CHDI Management/CHDI Foundation, Princeton, New Jersey, USA</aff><aff id="A82"><label>82</label>Section of Computational Biomedicine, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA</aff><aff id="A83"><label>83</label>Institute of Epidemiology and Biobank Popgen, Kiel University, Kiel, Germany</aff><aff id="A84"><label>84</label>Neurology Unit, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK</aff><aff id="A85"><label>85</label>University of North Carolina at Chapel Hill, Department of Epidemiology, Chapel Hill, North Carolina, USA</aff><aff id="A86"><label>86</label>Department of Public Health and Clinical Nutrition, University of Eastern Finland, Finland</aff><aff id="A87"><label>87</label>Research Unit, Kuopio University Hospital, Kuopio, Finland</aff><aff id="A88"><label>88</label>Institute of Biomedicine/Physiology, University of Eastern Finland, Kuopio Campus, Finland</aff><aff id="A89"><label>89</label>Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland</aff><aff id="A90"><label>90</label>Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK</aff><aff id="A91"><label>91</label>Faculty of Medicine, University of Split, Croatia</aff><aff id="A92"><label>92</label>Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden</aff><aff id="A93"><label>93</label>Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA</aff><aff id="A94"><label>94</label>Alzheimer Scotland Research Centre, University of Edinburgh, Edinburgh, UK</aff><aff id="A95"><label>95</label>Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK</aff><aff id="A96"><label>96</label>The Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands</aff><aff id="A97"><label>97</label>Division of Endocrinology, Boston Children’s Hospital, Boston, Massachusetts, USA</aff><aff id="A98"><label>98</label>Institute of Molecular and Cell Biology, Tartu, Estonia</aff><aff id="A99"><label>99</label>Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands</aff><aff id="A100"><label>100</label>Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands</aff><aff id="A101"><label>101</label>Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, The Netherlands</aff><aff id="A102"><label>102</label>Division of Nephrology, Department of Internal Medicine and Medical Specialties, Columbus - Gemelli University Hospital, Catholic University, Rome, Italy</aff><aff id="A103"><label>103</label>Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden</aff><aff id="A104"><label>104</label>Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California, USA</aff><aff id="A105"><label>105</label>Department of Medical Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands</aff><aff id="A106"><label>106</label>Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands</aff><aff id="A107"><label>107</label>Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, The Netherlands</aff><aff id="A108"><label>108</label>Department of Clinical Biochemistry, Lillebaelt Hospital, Vejle, Denmark</aff><aff id="A109"><label>109</label>Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark</aff><aff id="A110"><label>110</label>Medical Department, Lillebaelt Hospital, Vejle, Denmark</aff><aff id="A111"><label>111</label>Department of Clinical Immunology and Biochemistry, Lillebaelt Hospital, Vejle, Denmark</aff><aff id="A112"><label>112</label>South Ostrobothnia Central Hospital, Seinäjoki, Finland</aff><aff id="A113"><label>113</label>Tampere University Hospital, Tampere, Finland</aff><aff id="A114"><label>114</label>Imperial College Healthcare NHS Trust, London, UK</aff><aff id="A115"><label>115</label>National Heart and Lung Institute, Imperial College London, London, UK</aff><aff id="A116"><label>116</label>Institute of Reproductive and Developmental Biology, Imperial College London, London, UK</aff><aff id="A117"><label>117</label>Department of Epidemiology and Biostatistics, Medical Research Council Public Health England Centre for Environment and Health, School of Public Health, Faculty of Medicine, Imperial College London, St. Mary’s Campus, London, UK</aff><aff id="A118"><label>118</label>Centre for Life Course Epidemiology, Faculty of Medicine, University of Oulu, Oulu, Finland</aff><aff id="A119"><label>119</label>Biocenter Oulu, University of Oulu, Oulu, Finland</aff><aff id="A120"><label>120</label>Unit of Primary Care, Oulu University Hospital, Oulu, Finland</aff><aff id="A121"><label>121</label>Research Centre for Prevention and Health, Capital Region of Denmark, Copenhagen, Denmark</aff><aff id="A122"><label>122</label>Department of Clinical Experimental Research, Glostrup University Hospital, Glostrup, Denmark</aff><aff id="A123"><label>123</label>Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark</aff><aff id="A124"><label>124</label>Dasman Diabetes Institute, Dasman, Kuwait</aff><aff id="A125"><label>125</label>Centre for Vascular Prevention, Danube-University Krems, Krems, Austria</aff><aff id="A126"><label>126</label>King Abdulaziz University, Jeddah, Saudi Arabia</aff><aff id="A127"><label>127</label>School of Molecular, Genetic and Population Health Sciences, University of Edinburgh, Medical School, Teviot Place, Edinburgh, UK</aff><aff id="A128"><label>128</label>HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger, Norway</aff><aff id="A129"><label>129</label>St. Olav Hospital, Trondheim University Hospital, Trondheim, Norway</aff><aff id="A130"><label>130</label>Department of Medicine, Levanger Hospital, Nord- Trøndelag Health Trust, Levanger, Norway</aff><aff id="A131"><label>131</label>Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, USA</aff><aff id="A132"><label>132</label>Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, USA</aff><aff id="A133"><label>133</label>Folkhälsan Research Centre, Helsinki, Finland; Department of Endocrinology, Helsinki University Central Hospital, Helsinki, Finland</aff><aff id="A134"><label>134</label>Institute for Molecular Medicine Finland University of Helsinki, Helsinki, Finland</aff><aff id="A135"><label>135</label>Department of Clinical Sciences, Diabetes and Endocrinology, Lund University Diabetes Centre, Malmö, Sweden</aff><aff id="A136"><label>136</label>Department of Primary Health Care, Vaasa Central Hospital, Vaasa, Finland</aff><aff id="A137"><label>137</label>Diabetes Center, Vaasa Health Care Center, Vaasa, Finland</aff><aff id="A138"><label>138</label>Psychiatric and Neurodevelopmental Genetics Unit, Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, USA</aff><aff id="A139"><label>139</label>Department of Public Health, University of Helsinki, Finland</aff><aff id="A140"><label>140</label>ICDDR, B; Mohakhali, Dhaka, Bangladesh</aff><aff id="A141"><label>141</label>National Institute of Cardiovascular Diseases, Sher-e-Bangla Nagar, Dhaka, Bangladesh</aff><aff id="A142"><label>142</label>International Centre for Circulatory Health, Imperial College London, UK</aff><aff id="A143"><label>143</label>Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland</aff><aff id="A144"><label>144</label>University of Lille, UMR1167, Risk Factors and Molecular Determinants of aging-related diseases, Lille, France</aff><aff id="A145"><label>145</label>Inserm, Lille, France</aff><aff id="A146"><label>146</label>Centre Hospitalier Universitaire Lille, Public Health, Lille, France</aff><aff id="A147"><label>147</label>Institut Pasteur de Lille, Lille, France</aff><aff id="A148"><label>148</label>Department of Epidemiology and Public Health, EA 3430, University of Strasbourg, Strasbourg, France</aff><aff id="A149"><label>149</label>Department of General and Interventional Cardiology, University Heart Center Hamburg, Germany</aff><aff id="A150"><label>150</label>University Medical Center Hamburg-Eppendorf, Hamburg, Germany</aff><aff id="A151"><label>151</label>Department of Epidemiology, UMR 1027- INSERM, Toulouse University-CHU Toulouse, Toulouse, France</aff><aff id="A152"><label>152</label>Director, UKCRC Centre of Excellence for Public Health, Queens University, Belfast, Northern Ireland</aff><aff id="A153"><label>153</label>Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany</aff><aff id="A154"><label>154</label>Department of Medicine I, University Hospital Grosshadern, Ludwig-Maximilians-Universität, Munich, Germany</aff><aff id="A155"><label>155</label>DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany</aff><aff id="A156"><label>156</label>Research Center in Epidemiology and Preventive Medicine, Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy</aff><aff id="A157"><label>157</label>Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah, Saudi Arabia</aff><aff id="A158"><label>158</label>Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA</aff><aff id="A159"><label>159</label>Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA</aff><aff id="A160"><label>160</label>A Collaboration between the University Medical Schools and NHS, Aberdeen, Dundee, Edinburgh and Glasgow, UK</aff><aff id="A161"><label>161</label>Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA</aff><aff id="A162"><label>162</label>Institute of Cardiovascular Sciences, University of Manchester, Manchester, UK</aff><aff id="A163"><label>163</label>Faculty of Population Health Sciences, Institute of Cardiovascular Science, University College London, London, UK</aff><aff id="A164"><label>164</label>The Big Data Institute at the Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK</aff><aff id="A165"><label>165</label>Wellcome Trust Sanger Institute, Hinxton, UK</aff><aff id="A166"><label>166</label>The National Institute for Health Research Blood and Transplant Research</aff><author-notes><corresp id="CR1">Corresponding authors: Joanna M M Howson, <email>jmmh2@medschl.cam.ac.uk</email> and Patricia B Munroe, <email>p.b.munroe@qmul.ac.uk</email></corresp><fn id="FN1"><label>168</label><p id="P1">Jointly supervised the work</p></fn></author-notes><pub-date pub-type="nihms-submitted"><day>16</day><month>9</month><year>2016</year></pub-date><pub-date pub-type="epub"><day>12</day><month>9</month><year>2016</year></pub-date><pub-date pub-type="ppub"><month>10</month><year>2016</year></pub-date><pub-date pub-type="pmc-release"><day>12</day><month>3</month><year>2017</year></pub-date><volume>48</volume><issue>10</issue><fpage>1151</fpage><lpage>1161</lpage><pmc-comment>elocation-id from pubmed: 10.1038/ng.3654</pmc-comment>
<permissions><license><license-p>Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:<ext-link ext-link-type="uri" xlink:href="http://www.nature.com/authors/editorial_policies/license.html#terms">http://www.nature.com/authors/editorial_policies/license.html#terms</ext-link></license-p></license></permissions><abstract><p id="P2">High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to ~192,000 individuals, and used ~155,063 samples for independent replication. We identified 31 novel blood pressure or hypertension associated genetic regions in the general population, including three rare missense variants in <italic>RBM47</italic>, <italic>COL21A1</italic> and <italic>RRAS</italic> with larger effects (>1.5mmHg/allele) than common variants. Multiple rare, nonsense and missense variant associations were found in <italic>A2ML1</italic> and a low-frequency nonsense variant in <italic>ENPEP</italic> was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention.</p></abstract></article-meta></front><body><sec sec-type="intro" id="S1"><title>Introduction</title><p id="P3">High blood pressure (BP) or hypertension is a highly prevalent chronic disorder. It is estimated to be responsible for a larger proportion of global disease burden and premature mortality than any other disease risk factor<xref rid="R1" ref-type="bibr">1</xref>. Elevated systolic and/or diastolic BP increases the risk of several cardiovascular disorders including stroke, coronary heart disease (CHD), heart failure, peripheral arterial disease and abdominal aortic aneurysms<xref rid="R2" ref-type="bibr">2</xref>. BP is a complex, heritable, polygenic phenotype for which genome-wide association studies (GWAS) have identified over 67 genetic regions associated with BP and/or hypertension to date<xref rid="R3" ref-type="bibr">3</xref>–<xref rid="R11" ref-type="bibr">11</xref>. These variants are common (minor allele frequency, MAF≥0.05), mostly map to intronic or intergenic regions, with the causal alleles and genes not readily identified due to linkage disequilibrium (LD)<xref rid="R4" ref-type="bibr">4</xref>,<xref rid="R5" ref-type="bibr">5</xref>, and explain only ~2% of trait variance<xref rid="R12" ref-type="bibr">12</xref>. Low-frequency (0.01<xref rid="R13" ref-type="bibr">13</xref>, and may help to explain the missing heritability, and identify causative genes as demonstrated previously<xref rid="R14" ref-type="bibr">14</xref>.</p><p id="P4">To identify novel coding variants and loci influencing BP traits and hypertension we performed the largest meta-analysis to date that included a total of ~350,000 individuals, directly genotyped with the Exome chip. The Exome chip contains ~240,000 mostly rare and low-frequency variants (<xref ref-type="sec" rid="S11">Methods</xref>). A single-variant discovery analysis was performed, and candidate SNVs were taken forward for validation using independent replication samples. Gene-based tests were used to identify BP associated genes harboring multiple rare variant associations. We next assessed whether the newly identified BP associated SNVs were associated with expression levels of nearby genes, and tested these variants in aggregate for a causal association of BP with other cardiovascular traits and risk factors. Our findings highlight the contribution of rare variants in the aetiology of blood pressure in the general population, and provide new insights into the pathophysiology of hypertension.</p></sec><sec sec-type="results" id="S2"><title>Results</title><sec id="S3"><title>Discovery of single variant BP associations</title><p id="P5">We genotyped 192,763 individuals from 51 studies, and assessed association of 242,296 SNVs with diastolic BP (DBP), systolic BP (SBP), pulse pressure (PP) and hypertension (HTN; <xref ref-type="supplementary-material" rid="SD4">Supplementary Tables 1, 2 and 3</xref>; <xref ref-type="sec" rid="S11">Methods</xref>). An overview of the SNV discovery study design is given in <xref ref-type="fig" rid="F1">Figure 1</xref>. A fixed effects meta-analysis for each trait was performed using study-level association summary statistics from i) samples of European (EUR) ancestry (up to 165,276 individuals), and ii) a trans-ethnic meta-analysis of the EUR and additional South Asian (SAS) ancestry samples (EUR_SAS; up to 192,763 individuals). Two analyses of DBP, SBP and PP were performed, one in which the trait was inverse normal transformed and a second in which the raw phenotype was analysed. Both sets of results were consistent (<xref ref-type="sec" rid="S11">Methods</xref>), therefore to minimise sensitivity to deviations from normality in the analysis of rare variants, the results from the analyses of the transformed traits were used for discovery. Strong correlations between the BP traits were observed across studies (<xref ref-type="sec" rid="S11">Methods</xref>), hence no adjustment of significance thresholds for independent trait testing was applied.</p><p id="P6">The discovery meta-analyses identified 51 genomic regions with
genome-wide significant (GWS) evidence of association with at least one of the
four BP traits tested (<italic>P</italic><5x10<sup>-8</sup>; <xref ref-type="supplementary-material" rid="SD4">Supplementary Table 4</xref>).
There were 46 regions associated in the EUR_SAS samples, of which 14 were novel
(<xref ref-type="supplementary-material" rid="SD1">Supplementary Figure
1</xref>). An additional five regions were GWS in the EUR only meta-analyses
of which three were novel (<xref ref-type="supplementary-material" rid="SD1">Supplementary Figure 2</xref>). In total, 17 genomic regions were
identified that were GWS for at least one BP trait that have not been previously
reported.</p></sec><sec id="S4"><title>Replication of single variant BP associations</title><p id="P7">Next we sought support for our findings, in an independent replication dataset comprising
of 18 studies, 15 of which were from the Cohorts for Heart and Aging Research in
Genomic Epidemiology+ (CHARGE+) exome chip blood pressure consortium (<xref ref-type="fig" rid="F1">Figure 1</xref>; Liu <italic>et al.</italic> Nature
Genetics, <italic>submitted</italic>). Variants were selected for replication
first using the larger (transformed) EUR_SAS data, with additional variants from
the (transformed) EUR data also selected. SNVs were selected if they mapped
outside of known BP genomic regions and had MAF≥0.05 and
<italic>P</italic><1x10<sup>-5</sup> or MAF<0.05 and
<italic>P</italic><1x10<sup>-4</sup> with at least one BP trait,
<italic>i.e.</italic> choosing a lower significance threshold for the
selection of rare variants (full details of the selection criteria are provided
in the <xref ref-type="sec" rid="S11">Methods</xref>). In total 81 candidate
SNVs were selected for replication (<xref ref-type="supplementary-material" rid="SD4">Supplementary Table 5</xref>). Eighty variants were selected from
EUR_SAS (transformed) results and one SNV at the <italic>ZNF101</italic> locus
from the EUR (transformed) analyses. The results for EUR_SAS and EUR were
consistent (association statistics were correlated, ρ=0.9 across
ancestries for each of the traits). Of the 81 variants, 30 SNVs were selected
for association with DBP as the primary trait, 26 for SBP, 19 for PP and 6 for
HTN, with the primary trait defined as the BP trait with the smallest
association <italic>P</italic>-value in the EUR-SAS discovery analyses.</p><p id="P8">Meta-analyses were performed on results from analyses of untransformed DBP, SBP, PP and HTN (as only results of untransformed traits were available from CHARGE+) in (i) up to 125,713 individuals of EUR descent, and (ii) up to 155,063 individuals of multiple ethnicities (4,632 of Hispanic descent, 22,077 of African American descent, 2,641 SAS samples with the remainder EUR; <xref ref-type="fig" rid="F1">Figure 1</xref>). Given that a large proportion of the ancestries in the trans-ethnic meta-analyses were not included in our discovery samples, we used the EUR meta-analyses as the main data set for replication, but we also report any additional associations identified within the larger trans-ethnic dataset.</p><p id="P9">Novel BP-SNV associations were identified based on two criteria (<xref ref-type="fig" rid="F1">Figure 1</xref>; <xref ref-type="sec" rid="S11">Methods</xref>). Firstly, replication of the primary BP trait-SNV association was sought at a Bonferroni adjusted <italic>P</italic>-value threshold in the replication data (<italic>P</italic>≤6.17x10<sup>-4</sup>, assuming α=0.05 for 81 SNVs tested and same direction of effect; <xref ref-type="sec" rid="S11">Methods</xref>) without the need for GWS. Secondly, meta-analyses of discovery and replication results across all four (untransformed) BP traits were performed to assess the overall level of support across all samples for the 81 candidate SNVs; those BP-SNV associations that were GWS (with statistical support in the replication studies; <italic>P</italic><0.05 and the same direction of effect) were also declared as novel.</p><p id="P10">Seventeen SNV-BP associations formally replicated with concordant direction of effect at a Bonferroni adjusted significance level for the primary trait. Fourteen were in the EUR meta-analyses, and amongst these was a rare non-synonymous (ns) SNV mapping to <italic>COL21A1</italic> (<xref ref-type="table" rid="T1">Table 1</xref>, <xref ref-type="supplementary-material" rid="SD4">Supplementary Table 6</xref>). Three associations were in the trans-ethnic meta-analyses, these included two rare nsSNVs in <italic>RBM47</italic> and <italic>RRAS</italic> (<xref ref-type="table" rid="T1">Table 1</xref>, <xref ref-type="supplementary-material" rid="SD4">Supplementary Table 7</xref>; <xref ref-type="sec" rid="S11">Methods</xref>).</p><p id="P11">In addition to the 17 SNV-BP trait associations that formally replicated, we identified 13 further SNV-associations that were GWS in the combined (discovery and replication) meta-analyses. Ten of these were GWS in the combined EUR analyses, (<xref ref-type="table" rid="T2">Table 2</xref>; <xref ref-type="supplementary-material" rid="SD4">Supplementary Tables 6 and 8a</xref>), and three were GWS in the combined trans-ethnic meta-analyses (<xref ref-type="table" rid="T2">Table 2</xref>; <xref ref-type="supplementary-material" rid="SD4">Supplementary Tables 7 and 8b</xref>).</p><p id="P12">This gives a total of 30 novel SNV-BP associations (15 SNV-DBP, 9 SNV-SBP and 6 SNV-PP; <xref ref-type="table" rid="T1">Tables 1</xref> and <xref ref-type="table" rid="T2">2</xref>; <xref ref-type="supplementary-material" rid="SD1">Supplementary Figures 3 and 4</xref>). Five of the SNVs were GWS with more than one BP trait (<xref ref-type="fig" rid="F2">Figure 2</xref>: <xref ref-type="table" rid="T1">Tables 1</xref> and <xref ref-type="table" rid="T2">2</xref>; <xref ref-type="supplementary-material" rid="SD4">Supplementary Table 8</xref>). Four loci (<italic>CERS5</italic>, <italic>TBX2</italic>, <italic>RGL3</italic> and <italic>OBFC1</italic>) had GWS associations with HTN in addition to GWS associations with DBP and SBP. The <italic>PRKAG1</italic> locus had GWS associations with both SBP and PP.</p><p id="P13">Conditional analyses were performed to identify secondary signals of association within the novel BP loci. The RAREMETALWORKER (RMW) package (<xref ref-type="sec" rid="S11">Methods</xref>)<xref rid="R15" ref-type="bibr">15</xref> allows conditional analyses to be performed using summary level data. Hence, analyses of the transformed primary traits and HTN were re-run in RMW across the discovery studies (<xref ref-type="fig" rid="F3">Figure 3</xref>). The results of the RMW single variant tests were consistent with the initial discovery analyses (<xref ref-type="supplementary-material" rid="SD2">Supplementary Information</xref>). Given the RMW analyses were based on our discovery samples, the larger EUR-SAS data was used as the main analysis to increase power, but we also report any additional associations with evidence in EUR.</p><p id="P14">We identified secondary independent signals of association in four loci, <italic>PREX1, PRKAG1</italic> and <italic>RRP1B</italic> within the EUR_SAS analyses and <italic>COL21A1</italic> in the EUR analyses (<italic>P</italic><sub>conditional</sub><1x10<sup>-4</sup>, Bonferroni adjusted for ~500 variants within each region; <xref ref-type="sec" rid="S11">Methods</xref>; <xref ref-type="supplementary-material" rid="SD4">Supplementary Tables 9 and 10</xref>). Three independent association signals were identified in the <italic>MYH6</italic> locus in the EUR_SAS analyses (<xref ref-type="supplementary-material" rid="SD4">Supplementary Table 11</xref>).</p></sec><sec id="S5"><title>Gene-based BP associations</title><p id="P15">To improve statistical power to detect associations in genes harbouring rare variants, analytical methods that combine effects of variants across a gene into a single test have been devised and are implemented in the RMW package<xref rid="R15" ref-type="bibr">15</xref>. We applied the gene-based sequence kernel association test (SKAT)<xref rid="R16" ref-type="bibr">16</xref> and Burden tests<xref rid="R17" ref-type="bibr">17</xref> to the RMW dataset (MAF<0.05 or MAF<0.01; <xref ref-type="fig" rid="F3">Figure 3</xref>; <xref ref-type="sec" rid="S11">Methods</xref>). One previously unidentified BP gene (<italic>A2ML1</italic>) was associated with HTN (<italic>P</italic>= 7.73x10<sup>-7</sup>) in the EUR_SAS studies and also in EUR studies (<xref ref-type="supplementary-material" rid="SD4">Supplementary Table 12</xref>; Bonferroni-corrected threshold of significance <italic>P</italic><2.8x10<sup>-6</sup>, after adjusting for 17,996 genes tested, <xref ref-type="sec" rid="S11">Methods</xref>). The gene showed residual association with the primary BP trait after conditioning on the most associated SNV in the gene (<italic>P</italic><sub>conditional</sub>=5.00x10<sup>-4</sup>; <xref ref-type="supplementary-material" rid="SD4">Supplementary Table 12</xref>), suggesting that the association is due to multiple rare variants in the gene. One nonsense variant (rs199651558, p.Arg893*, MAF=3.5x10<sup>-4</sup>) was observed, and there were multiple missense variants (<xref ref-type="fig" rid="F4">Figure 4</xref>). <italic>A2ML1</italic> encodes alpha-2-macroglobulin-like 1 protein, and is a member of the alpha macroglobulin superfamily, which comprises protease inhibitors targeting a wide range of substrates. Mutations in this gene are associated with a disorder clinically related to Noonan syndrome, a developmental disorder which involves cardiac abnormalities<xref rid="R18" ref-type="bibr">18</xref>. We sought replication in the CHARGE+ studies for this gene, however there was no evidence of association with HTN (<italic>P</italic>= 0.45). Given the very low frequencies of the variants involved, however, studies in which the variants are polymorphic will be required to replicate the association with HTN. The DBH gene was found to be associated with DBP using the SKAT test (<italic>P</italic>=2.88x10<sup>-6</sup>). However, this was not due to multiple rare variants as the association was driven by rs77273740 (<xref ref-type="supplementary-material" rid="SD4">Supplementary Table 5</xref>) and the SNV was not validated in the replication samples.</p></sec><sec id="S6"><title>Rare and common variant associations in established BP loci</title><p id="P16">Of the 67 established BP loci, 35 loci were on the Exome chip (N=43 SNVs or close proxies r<sup>2</sup>>0.7). All 43 SNVs had at least nominal evidence of association with BP in our discovery samples (<italic>P</italic><0.01; <xref ref-type="supplementary-material" rid="SD4">Supplementary Table 13</xref>). We also assessed if any of the established BP loci contained coding variants that are associated with BP traits and in LD (r<sup>2</sup>>0.2) with the known BP variants on the Exome chip (<xref ref-type="supplementary-material" rid="SD4">Supplementary Table 13</xref>), using the 1000G phase 3 release for LD annotation. Focusing on SNVs that were GWS for any BP trait from our transformed discovery data for either ancestry, there were 25 coding variants, of which 6 were predicted to be damaging at loci labelled <italic>CDC25A, SLC39A8, HFE, ULK4, ST7L-CAPZA1-MOV10</italic> and <italic>CYP1A1-ULK3</italic>. Three of these are published variants at loci labelled <italic>SLC39A8, HFE</italic> and <italic>ST7-CAPZA1-MOV10.</italic> At <italic>CYP1A1-ULK3</italic>, the coding variant was in moderate LD with the reported variant, but was less significantly associated with DBP in our EUR_SAS dataset (<italic>P</italic>=2.24x10<sup>-8</sup> compared to <italic>P</italic>=1.68x10<sup>-15</sup> for the published variant). At the <italic>ULK4</italic> locus the predicted damaging coding variant had similar association as the published coding variant (predicted to be benign), and prior work has already indicated several associated nsSNVs in strong LD in <italic>ULK4</italic><xref rid="R19" ref-type="bibr">19</xref>. The nsSNV within the <italic>CDC25A</italic> locus (rs11718350 in <italic>SPINK8</italic>) had similar association with DBP as the intergenic published SNV in our EUR_SAS dataset (<italic>P</italic>=2.00x10<sup>-8</sup> compared to <italic>P=</italic>2.27x10<sup>-8</sup> for the published variant). Overall at least 5 of the known loci are consistent with having a coding causal variant.</p><p id="P17">Gene-based SKAT tests of all genes that map within 1 Mb of a previously reported SNV association (<xref ref-type="supplementary-material" rid="SD4">Supplementary Table 14</xref>), indicated no genes with multiple rare or low-frequency variant associations. Single variant conditional analyses showed that rs33966350, a rare nonsense variant in <italic>ENPEP</italic> (MAF=0.01) was associated with SBP (<italic>P</italic><sub>conditional</sub>=1.61x10<sup>-5</sup>) in the EUR_SAS samples (<xref ref-type="supplementary-material" rid="SD4">Supplementary Tables 14 and 15</xref>; <xref ref-type="sec" rid="S11">Methods</xref>) independently of the known SNV (rs6825911). <italic>ENPEP</italic> encodes aminopeptidase A (APA) an enzyme of the renin-angiotensin-aldosterone system (RAAS) that converts angiotensin II (AngII) to AngIII.</p><p id="P18">There were no other established loci with convincing low-frequency or rare SNV associations in the EUR_SAS samples. However, <italic>HOXC4</italic>, had evidence of a second independent signal with a rare missense SNV in EUR samples (rs78731604; MAF=0.005, <italic>P</italic><sub>conditional</sub>= 5.76x10<sup>-5</sup>; <xref ref-type="supplementary-material" rid="SD4">Supplementary Table 15</xref>). The secondary signal in the <italic>HOXC4</italic> region, mapped to <italic>CALCOCO1</italic>, ~300kb from the known SNV. The gene association (MAF≤0.01, <italic>P</italic>=2.37x10<sup>-5</sup>) was below the required significance threshold and attributable to rs78731604, which is not predicted to have detrimental effects on protein structure. Therefore, replication of this association is required. Three loci (<italic>ST7L-CAPZA1-MOV10, FIGN-GRB14,</italic> and <italic>TBX5-TBX3</italic>) had evidence of a second independent signal in the region in EUR_SAS samples with a common variant (<italic>P</italic><sub>conditional</sub><1x10<sup>-4</sup>; <xref ref-type="supplementary-material" rid="SD4">Supplementary Table 15</xref>) that has not been previously reported.</p><p id="P19">Having identified 30 novel loci associated with BP traits, as well as additional new independent SNVs at four novel loci and five known loci, we calculated the percent of the trait variance explained (<xref ref-type="sec" rid="S11">Methods</xref>). This was 2.08%/2.11%/1.15% for SBP/DBP/PP for the 43 previously reported BP-SNVs covered in our dataset, increasing to 3.38%/3.41%/2.08% respectively with the inclusion of the 30 lead SNVs from novel loci, plus new independent SNV-BP associations identified from novel and known loci.</p></sec><sec id="S7"><title>Effect of BP SNVs on cardiovascular traits & risk factors</title><p id="P20">Amongst our novel BP-SNV associations, some have previously been reported to be associated with other cardiovascular traits and risk factors (<xref ref-type="supplementary-material" rid="SD4">Supplementary Table 16</xref>); these include coronary heart disease (CHD: <italic>PHACTR1</italic>, <italic>ABO</italic>)<xref rid="R20" ref-type="bibr">20</xref>,<xref rid="R21" ref-type="bibr">21</xref>, QT interval (<italic>RNF207</italic>)<xref rid="R22" ref-type="bibr">22</xref>, heart rate (<italic>MYH6</italic>)<xref rid="R23" ref-type="bibr">23</xref>, and cholesterol levels (2q36.3, <italic>ABO</italic>, <italic>ZNF101</italic>)<xref rid="R24" ref-type="bibr">24</xref>.</p><p id="P21">To test the impact of BP variants on cardiovascular endpoints and risk factors we created three weighted genetic risk scores (GRS) according to SBP/DBP/PP based on the newly identified and previously published BP variants (up to N=125; <xref ref-type="sec" rid="S11">Methods</xref>). The GRS models were used to test the causal effect of BP on the following traits: ischemic stroke (including the subtypes, cardiometabolic, large and small vessel <xref rid="R25" ref-type="bibr">25</xref>), CHD, heart failure,<xref rid="R26" ref-type="bibr">26</xref> left ventricular mass<xref rid="R27" ref-type="bibr">27</xref>, left ventricular wall thickness<xref rid="R27" ref-type="bibr">27</xref>, high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein (LDL-c), triglycerides, total cholesterol, body mass index (BMI), waist-hip ratio adjusted BMI, height and estimated glomerular filtration rate (eGFR) (<xref ref-type="sec" rid="S11">Methods</xref>). As expected, BP was positively associated with increased CHD risk (OR [95% CI]=1.39[1.22-1.59] per 10mmHg increase in SBP, <italic>P</italic>=6.07×10<sup>-7</sup>; 1.62[1.28-2.05] per 10mmHg increase in DBP, <italic>P</italic>=5.99x10<sup>-5</sup>; 1.70[1.34-2.16] per 10mmHg increase in PP, <italic>P</italic>=1.20x10<sup>-5</sup>; <xref ref-type="table" rid="T3">Table 3</xref>), and increased risk of ischemic stroke (OR [95% CI]=1.93[1.47-2.55] per 10mmHg increase in DBP, <italic>P</italic>=2.81×10<sup>-6</sup>; 1.57[1.35-1.84] per 10mmHg increase in SBP, <italic>P</italic>=1.16×10<sup>-8</sup>; 2.12[1.58-2.84] per 10mmHg increase in PP, <italic>P</italic>=5.35x10<sup>-7</sup>). The positive association with ischemic stroke was primarily due to large vessel stroke (<xref ref-type="table" rid="T3">Table 3</xref>). DBP and SBP were also positively associated with left ventricular mass (9.57 [3.98-15.17] gram increase per 10mmHg increase in DBP, <italic>P</italic>=8.02x10<sup>-4</sup> and 5.13 [1.77-8.48] gram increase per 10mmHg increase in SBP, <italic>P</italic>=0.0027) and left ventricular wall thickness (0.10 [0.06-0.13] cm increase per 10mmHg increase in DBP, <italic>P</italic>=1.88x10<sup>-8</sup> and 0.05 [0.03-0.07] cm increase per 10mmHg increase in SBP, <italic>P</italic>=5.52x10<sup>-6</sup>, <xref ref-type="table" rid="T3">Table 3</xref>). There was no convincing evidence to support the BP associated variants having an effect on lipid levels (<italic>P</italic>>0.1), BMI (<italic>P</italic>>0.005), waist hip ratio adjusted BMI (<italic>P</italic>>0.1), height (<italic>P</italic>>0.06), eGFR (<italic>P</italic>>0.02) or heart failure (<italic>P</italic>>0.04). The causal associations with CHD, stroke, and left ventricular measures augment the results from a previous association analysis using 29 BP variants<xref rid="R28" ref-type="bibr">28</xref>. Our data strongly support the previous observations of no causal relationship between BP and eGFR. Lack of evidence of a BP effect with heart failure may only be due to lack of power, as the association was in the expected direction.</p></sec><sec id="S8"><title>Possible functional variants at BP loci and candidate genes</title><p id="P22">Twenty-six of our newly discovered BP associated SNVs had MAF≥0.05 and therefore due to extensive LD with other SNVs not genotyped on the Exome array, identifying the causal genes requires additional information. If a SNV is associated with increased or decreased expression of a particular gene, <italic>i.e.</italic> it is an expression quantitative trait locus (eQTL) this suggests the gene on which the SNV acts could be in the causal pathway. To help identify potential candidate causal genes in the novel BP loci (<xref ref-type="supplementary-material" rid="SD4">Supplementary Table 9</xref>), information from publicly available eQTL databases was investigated (MuTHER for LCL, adipose and skin and GTEx for nine tissues including the heart and tibial artery; <xref ref-type="sec" rid="S11">Methods</xref>).</p><p id="P23">The DBP increasing allele of the nsSNV, rs7302981-A, was associated with increased expression of <italic>CERS5</italic> in: LCLs (<italic>P</italic><sub>MuTHER</sub>=3.13x10<sup>-72</sup>) skin (<italic>P</italic><sub>MuTHER</sub>=2.40x10<sup>-58</sup>) adipose (<italic>P</italic><sub>MuTHER</sub>=2.87x10<sup>-54</sup>) and nerve (<italic>P</italic><sub>GTEx</sub>=4.5x10<sup>-12</sup>) (<xref ref-type="supplementary-material" rid="SD1">Supplementary Figure 5</xref>). Additional testing (<xref ref-type="sec" rid="S11">Methods</xref>) provided no evidence against colocalisation of the eQTL and DBP association signals, implicating <italic>CERS5</italic> as a candidate causal gene for this DBP locus. <italic>CERS5</italic> (LAG1 homolog, ceramide synthase 5) is involved in the synthesis of ceramide, a lipid molecule involved in several cellular signaling pathways. <italic>Cers5</italic> knockdown has been shown to reduce cardiomyocyte hypertrophy in mouse models<xref rid="R29" ref-type="bibr">29</xref>. However, it is unclear whether the blood pressure raising effects at this locus are the cause or result of any potential effects on cardiac hypertrophy. Future studies investigating this locus in relation to parameters of cardiac hypertrophy and function (<italic>e.g.</italic> ventricular wall thickness) should help address this question.</p><p id="P24">The DBP raising allele of the nsSNV (rs867186-A) was associated with increased expression of <italic>PROCR</italic> in adipose tissue (<italic>P</italic><sub>MuTHER</sub>=3.24x10<sup>-15</sup>) and skin (<italic>P</italic><sub>MuTHER</sub>=1.01x10<sup>-11</sup>) (<xref ref-type="supplementary-material" rid="SD1">Supplementary Figure 5</xref>). There was no evidence against colocalisation of the eQTL and DBP association thus supporting <italic>PROCR</italic> as a candidate causal gene. <italic>PROCR</italic> encodes the Endothelial Protein C receptor, a serine protease involved in the blood coagulation pathway, and rs867186 has previously been associated with coagulation and haematological factors.<xref rid="R30" ref-type="bibr">30</xref>,<xref rid="R31" ref-type="bibr">31</xref> The PP decreasing allele of, rs10407022-T, which is predicted to have detrimental effects on protein structure (<xref ref-type="sec" rid="S11">Methods</xref>) was associated with increased expression of <italic>AMH</italic> in muscle (<italic>P</italic><sub>GTEx</sub>=9.95x10<sup>-15</sup>), thyroid (<italic>P</italic><sub>GTEx</sub>=8.54x10<sup>-7</sup>), nerve (<italic>P</italic><sub>GTEx</sub>=7.15x10<sup>-8</sup>), tibial artery (<italic>P</italic><sub>GTEx</sub>=6.46x10<sup>-9</sup>), adipose (<italic>P</italic><sub>GTEx</sub>=4.69x10<sup>-7</sup>), and skin (<italic>P</italic><sub>GTEx</sub>=5.88x10<sup>-8</sup>) (<xref ref-type="supplementary-material" rid="SD1">Supplementary Figure 5</xref>). There was no evidence against colocalisation of the eQTL and PP association, which supports <italic>AMH</italic> as a candidate causal gene for PP. Low AMH levels have been previously associated with hypertensive status in women with the protein acting as a marker of ovarian reserve<xref rid="R32" ref-type="bibr">32</xref>. The intergenic SBP raising allele of rs4728142-A was associated with reduced expression of <italic>IRF5</italic> in skin (<italic>P</italic><sub>MuTHER</sub>=5.24x10<sup>-31</sup>) and LCLs (<italic>P</italic><sub>MuTHER</sub>=1.39x10<sup>-34</sup>), whole blood (<italic>P</italic><sub>GTEx</sub>=3.12x10<sup>-7</sup>) and tibial artery (<italic>P</italic><sub>GTEx</sub>=1.71x10<sup>-7</sup>).</p><p id="P25">Three novel rare nsSNVs were identified that map to <italic>RBM47</italic>, <italic>RRAS</italic> (both associated with SBP) and <italic>COL21A1</italic> (associated with PP). They had larger effect sizes than common variant associations (>1.5mmHg per allele; <xref ref-type="supplementary-material" rid="SD1">Supplementary Figure 6</xref>) and were predicted to have detrimental effects on protein structure (<xref ref-type="supplementary-material" rid="SD4">Supplementary Table 16</xref>; <xref ref-type="sec" rid="S11">Methods</xref>). In <italic>RBM47</italic>, rs35529250 (p.Gly538Arg) is located in a highly conserved region of the gene and was most strongly associated with SBP (MAF=0.008; +1.59 mmHg per T allele; <italic>P</italic>=5.90x10<sup>-9</sup>). <italic>RBM47</italic> encodes the RNA binding motif protein 47 and is responsible for post-transcriptional regulation of RNA, through its direct and selective binding with the molecule.<xref rid="R33" ref-type="bibr">33</xref> In <italic>RRAS</italic>, rs61760904 (p.Asp133Asn) was most strongly associated with SBP (MAF=0.007; +1.51 mmHg per T allele; <italic>P</italic>=8.45x10<sup>-8</sup>). <italic>RRAS</italic> encodes a small GTPase belonging to the Ras subfamily of proteins H-RAS, N-RAS, and K-RAS and has been implicated in actin cytoskeleton remodelling, and controlling cell proliferation, migration and cycle processes<xref rid="R34" ref-type="bibr">34</xref>. The nsSNV in <italic>COL21A1</italic> (rs200999181, p.Gly665Val) was most strongly associated with PP (MAF=0.001; +3.14 mmHg per A allele; <italic>P</italic>=1.93x10<sup>-9</sup>). <italic>COL21A1</italic> encodes the collagen alpha-1 chain precursor of type XXI collagen, a member of the FACIT (fibril-associated collagens with an interrupted triple helix) family of proteins<xref rid="R35" ref-type="bibr">35</xref>. The gene is detected in many tissues, including the heart and aorta. Based on our results, these three genes represent good candidates for functional follow-up. However, due to the incomplete coverage of all SNVs across the region on the Exome chip, it is possible that other non-genotyped SNVs may better explain some of these associations. We therefore checked for variants in LD (r<sup>2</sup>>0.3) with these three rare nsSNVs in the UK10K + 1000G dataset<xref rid="R36" ref-type="bibr">36</xref> to ascertain if there are other candidate SNVs at these loci (<xref ref-type="supplementary-material" rid="SD4">Supplementary Table 17</xref>). There were no SNVs within 1Mb of the <italic>RBM47</italic> locus in LD with the BP associated SNV. At the <italic>COL21A</italic>1 locus there were only SNVs in moderate LD, and these were annotated as intronic, intergenic or in the 5’UTR. At the <italic>RRAS</italic> locus, there were two SNVs in strong LD with the BP associated SNV, which both mapped to introns of <italic>SCAF1</italic> and are not predicted to be damaging. All SNVs in LD at both loci were rare as expected (<xref ref-type="supplementary-material" rid="SD4">Supplementary Table 17</xref>) supporting a role for rare variants. Hence, the rare BP associated nsSNVs at <italic>RBM47, COL21A1</italic> an<italic>d RRAS</italic> remain the best causal candidates.</p></sec><sec id="S9"><title>Pathway and network analyses</title><p id="P26">To identify connected gene sets and pathways implicated by the BP associated genes we used Meta-Analysis Gene-set Enrichment of variant Associations (MAGENTA)<xref rid="R37" ref-type="bibr">37</xref> and GeneGo MetaCore (Thomson Reuters, UK). MAGENTA tests for over-representation of BP associated genes in pre-annotated pathways (gene sets) (<xref ref-type="sec" rid="S11">Methods</xref> and <xref ref-type="supplementary-material" rid="SD4">Supplementary Table 18a</xref>). GeneGo Metacore identifies potential gene networks. The MAGENTA analysis was used for hypothesis generation and results were compared with the GeneGo Metacore outputs to cross-validate findings.</p><p id="P27">Using MAGENTA there was an enrichment (<italic>P</italic><0.01 and FDR<5% in either the EUR_SAS or the EUR participants) of six gene sets with DBP, three gene sets with HTN and two gene sets for SBP (<xref ref-type="supplementary-material" rid="SD4">Supplementary Table 18b</xref>). The RNA polymerase I promoter clearance (chromatin modification) pathway showed the most evidence of enrichment with genes associated with DBP (<italic>P</italic><sub>Reactome</sub>=8.4x10<sup>-5</sup>, FDR=2.48%). NOTCH signalling was the most associated pathway with SBP (<italic>P</italic><sub>Reactome</sub> = 3.00x10<sup>-4</sup>, FDR = 5%) driven by associations at the <italic>FURIN</italic> gene. The inorganic cation anion solute carrier (SLC) transporter pathway had the most evidence of enrichment by HTN associated genes (<italic>P</italic><sub>Reactome</sub>=8.00x10<sup>-6</sup>, FDR=2.13%).</p><p id="P28">Using GeneGo MetaCore, five network processes were enriched (FDR<5%; <xref ref-type="sec" rid="S11">Methods</xref>; <xref ref-type="supplementary-material" rid="SD4">Supplementary Tables 19 and 20</xref>). These included several networks with genes known to influence vascular tone and BP: inflammation signalling, <italic>P</italic>=1.14x10<sup>-4</sup> and blood vessel development <italic>P</italic>=2.34x10<sup>-4</sup>. The transcription and chromatin modification network (<italic>P</italic>=2.85x10<sup>-4</sup>) was also enriched, a pathway that was also highlighted in the MAGENTA analysis, with overlap of the same histone genes (<italic>HIST1H4C</italic>, <italic>HIST1H2AC</italic>, <italic>HIST1H2BC</italic>, <italic>HIST1H1T</italic>) and has also been recently reported in an integrative network analysis of published BP loci and whole blood expression profiling<xref rid="R38" ref-type="bibr">38</xref>. Two cardiac development pathways were enriched: the oxidative stress-driven (ROS/NADPH) (<italic>P</italic>=4.12x10<sup>-4</sup>) and the Wnt/β-catenin/integrin-driven (<italic>P</italic>=0.0010). Both these cardiac development pathways include the <italic>MYH6</italic>, <italic>MYH7</italic>, and <italic>TBX2</italic> genes, revealing a potential overlap with cardiomyopathies and hypertension, and suggesting some similarity in the underlying biological mechanisms.</p></sec></sec><sec sec-type="discussion" id="S10"><title>Discussion</title><p id="P29">By conducting the largest ever genetic study of BP, we identified further novel common variants with small effects on BP traits, similar to what has been observed for obesity and height<xref rid="R39" ref-type="bibr">39</xref>,<xref rid="R40" ref-type="bibr">40</xref>. More importantly, our study identified some of the first rare coding variants of strong effect (>1.5mmHg) that are robustly associated with BP traits in the general population, complementing and extending the previous discovery and characterisation of variants underlying rare Mendelian disorders of blood pressure regulation <xref rid="R41" ref-type="bibr">41</xref>. Using SNV associations in 17 genes reported to be associated with monogenic disorders of blood pressure (<xref ref-type="sec" rid="S11">Methods</xref>) we found no convincing evidence of enrichment (<italic>P</italic><sub>enrichment</sub>=0.044). This suggests that BP control in the general population may occur through different pathways to monogenic disorders of BP re-enforcing the importance of our study findings. The identification of 30 novel BP loci plus further new independent secondary signals within four novel and five known loci (<xref ref-type="sec" rid="S11">Methods</xref>) has augmented the trait variance explained by 1.3%, 1.2% and 0.93% for SBP, DBP and PP respectively within our data-set. This suggests that with substantially larger sample sizes, for example through UK BioBank<xref rid="R42" ref-type="bibr">42</xref>, we expect to identify 1000s more loci associated with BP traits, and replicate more of our discovery SNV associations that are not yet validated in the current report.</p><p id="P30">The discovery of rare missense variants has implicated several interesting candidate genes, which are often difficult to identify from common variant GWAS, and should therefore lead to more rapidly actionable biology. <italic>A2ML1</italic>, <italic>COL21A1</italic>, <italic>RRAS</italic> and <italic>RBM47</italic> all warrant further follow-up studies to define the role of these genes in regulation of BP traits, as well as functional studies to understand their mechanisms of action. <italic>COL21A1</italic> and <italic>RRAS</italic> warrant particular interest since both are involved in blood vessel remodelling, a pathway of known aetiological relevance to hypertension.</p><p id="P31">We observed a rare nonsense SBP associated variant in <italic>ENPEP</italic> (rs33966350; p.Trp317* ): this overlaps a highly conserved region of both the gene and protein and is predicted to result in either a truncated protein with reduced catalytic function or is subject to nonsense mediated RNA decay. ENPEP converts angiotensin II (AngII) to Ang-III. AngII activates the angiotensin 1 (AT1) receptor resulting in vasoconstriction, while AngIII activates the angiotensin 2 (AT2) receptor that promotes vasodilation and protects against hypertension.<xref rid="R43" ref-type="bibr">43</xref> The predicted truncated protein may lead to predominant AngII signaling in the body, and increases in BP. This new observation could potentially inform therapeutic strategies. Of note, angiotensin-converting-enzyme (ACE) inhibitors are commonly used in the treatment of hypertension. However, patients who suffer from adverse reactions to ACE inhibitors, such as dry cough and skin rash, would benefit from alternative drugs that target RAAS. Murine studies have shown that in the brain, AngIII is the preferred AT1 agonist that promotes vasoconstriction and increases blood pressure, as opposed to AngII in the peripheral system. These results have motivated the development of brain specific APA inhibitors to treat hypertension<xref rid="R44" ref-type="bibr">44</xref>. Our results confirm APAs, such as ENPEP, as a valid target to modify blood pressure, but suggest that long-term systemic reduction in APA activity may lead to an increase in blood pressure. Future studies are needed to examine the effects of the p.Trp317* variant on the RAAS system, specifically in the brain and peripheral vasculature, in order to test the benefits of the proposed therapeutic strategy in humans.</p><p id="P32">In addition to highlighting new genes in pathways of established relevance to BP and hypertension, and identifying new pathways, we have also identified multiple signals at new loci. For example, there are three distinct signals at the locus containing the <italic>MYH6</italic>/<italic>MYH7</italic> genes, and we note that <italic>TBX2</italic> maps to one of the novel regions. These genes are related to cardiac development and/or cardiomyopathies, and provide an insight into the shared inheritance of multiple complex traits. Unravelling the causal networks within these polygenic pathways may provide opportunities for novel therapies to treat or prevent both hypertension and cardiomyopathies.</p></sec><sec sec-type="methods" id="S11" specific-use="web-only"><title>Online Methods</title><sec id="S12"><title>Overview of discovery studies</title><p id="P33">The cohorts contributing to the discovery meta-analyses comprise studies from three consortia (CHD Exome+, ExomeBP, and GoT2D/T2D-GENES) with a total number of 192,763 unique samples. All participants provided written informed consent and the studies were approved by their local Research Ethics Committees and/or Institutional Review Boards.</p><p id="P34">The CHD Exome+ consortium comprised 77,385 samples: eight studies (49,898 samples) of European (EUR) ancestry, two studies (27,487 samples) of South Asian (SAS) ancestry (<xref ref-type="supplementary-material" rid="SD4">Supplementary Table 1</xref>). The ExomeBP consortium included 25 studies (75,620 samples) of EUR ancestry (<xref ref-type="supplementary-material" rid="SD4">Supplementary Table 1</xref>). The GoT2D consortium comprised 14 studies (39,758 samples) of Northern EUR ancestry from Denmark, Finland, and Sweden (<xref ref-type="supplementary-material" rid="SD4">Supplementary Table 1</xref>). The participating studies and their characteristics including BP phenotypes are detailed in <xref ref-type="supplementary-material" rid="SD4">Supplementary Tables 1 and 2</xref>. Note, any studies contributing to multiple consortia were only included once in all meta-analyses.</p></sec><sec id="S13"><title>Phenotypes</title><p id="P35">Four blood pressure (BP) traits were analysed: systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP) and hypertension (HTN). For individuals known to be taking BP lowering medication, 15/10 mmHg was added to the raw SBP/DBP values, respectively, to obtain medication-adjusted SBP/DBP values<xref rid="R45" ref-type="bibr">45</xref>. PP was defined as SBP minus DBP, post-adjustment. For HTN, individuals were classified as hypertensive cases if they satisfied at least one of: (i) SBP≥140 mmHg, (ii) DBP≥90 mmHg, (iii) taking anti-hypertensive or BP lowering medication. All other individuals were included as controls. The four BP traits were correlated (SBP:DBP correlations were between 0.6 and 0.8, and SBP:PP correlations were ~0.8). However, they measure partly distinct physiological features including, cardiac output, vascular resistance, and arterial stiffness, all measures for determining a cardiovascular risk profile. Therefore the genetic architecture of the individual phenotypes are of interest, and a multi-phenotype mapping approach was not adopted.</p></sec><sec id="S14"><title>Genotyping</title><p id="P36">All samples were genotyped using one of the Illumina HumanExome Beadchip arrays (<xref ref-type="supplementary-material" rid="SD4">Supplementary Table 3</xref>). An Exome chip quality control Standard Operating Procedure (SOP) developed by Anubha Mahajan, Neil Robertson and Will Rayner at the Wellcome Trust Centre for Human Genetics, University of Oxford was used by most studies for genotype calling and QC<xref rid="R46" ref-type="bibr">46</xref> (<xref ref-type="supplementary-material" rid="SD4">Supplementary Table 3</xref>). All genotypes were aligned to the plus strand of the human genome reference sequence (Build37) prior to any analyses and any unresolved mappings were removed. Genotype cluster plots were reviewed for all the novel rare variants (both lead and secondary signals) and for rare variants that contributed to the gene-based testing.</p></sec><sec id="S15"><title>Meta-analyses</title><p id="P37">Meta-analyses were performed using METAL<xref rid="R47" ref-type="bibr">47</xref>, for both discovery and replication analyses, using inverse variance weighted fixed effect meta-analysis for the continuous traits (SBP, DBP and PP) and sample size weighted meta-analysis for the binary trait (HTN).</p></sec><sec id="S16"><title>Discovery SNV analyses</title><p id="P38">Analyses of both untransformed and inverse normal transformed SBP, DBP and PP were conducted within each contributing study. The analyses of the transformed traits were performed in order to minimise sensitivity to deviations from normality in the analysis of rare variants and for discovery of new SNV-BP associations. The residuals from the null model obtained after regressing the medication-adjusted trait on the covariates (age, age<sup>2</sup>, sex, BMI, and disease status for CHD) within a linear regression model, were ranked and inverse normalised. These normalised residuals were used to test trait-SNV associations. All SNVs that passed QC were analysed for association, without any further filtering by MAF, but a minor allele count of 10 was used for the analysis of HTN. An additive allelic effects model was assumed.</p><p id="P39">Two meta-analyses were performed for each trait, one with EUR and SAS ancestries combined (EUR_SAS) and another for EUR ancestry alone. Contributing studies used principal components (PCs) to adjust for population stratification. Consequently minimal inflation in the association test statistics, λ, was observed (λ=1.07 for SBP, 1.10 for DBP, 1.04 for PP and <1 for HTN in the transformed discovery meta-analysis in EUR_SAS; λ= 1.06 for SBP, 1.09 for DBP, 1.05 for PP and <1 for HTN in the transformed discovery meta-analysis in EUR; <xref ref-type="supplementary-material" rid="SD1">Supplementary Figure 7</xref>). The meta-analyses were performed independently in two centres and results were found to be concordant between centres. Given the studies contributing to the discovery analyses were ascertained on CHD or T2D, we tested potential systematic bias in calculated effect estimates amongst these studies. No evidence of bias in the overall effect estimates was obtained.</p><p id="P40">The results for the transformed traits were taken forward and used to select candidate SNVs for replication. Results (<italic>P</italic>-values) from the transformed and untransformed analyses were strongly correlated (r<sup>2</sup>>0.9).</p></sec><sec id="S17"><title>Replication SNV analyses</title><p id="P41">SNVs associated with any of the transformed traits (SBP, DBP, PP) or HTN were annotated using the Illumina SNV annotation file, humanexome-12v1_a_gene_annotation.txt, independently across two centres. Given the difference in power to detect common versus low frequency and rare variant associations, two different significance thresholds were chosen for SNV selection. For SNVs with MAF≥0.05, <italic>P</italic>≤1x10<sup>-5</sup> was selected, while, <italic>P</italic>≤1x10<sup>-4</sup> was used for SNVs with MAF < 0.05. By choosing a significance threshold of <italic>P</italic><1x10<sup>-4</sup> we maximized the opportunity to follow-up rare variants (making the assumption that any true signals at this threshold could replicate at Bonferroni adjusted significance, <italic>P</italic>≤6.17x10<sup>-4</sup>, assuming α=0.05 for 81 SNVs). All previously published BP associated SNVs and any variants in LD with them (r<sup>2</sup>>0.2), were removed from the list of associated SNVs as we aimed to replicate new findings only. SNVs for which only one study contributed to the association result or showed evidence of heterogeneity (<italic>P</italic><sub>het</sub><0.0001) were removed from the list as they were likely to be an artefact. Where SNVs were associated with multiple traits, to minimise the number of tests performed, only the trait with the smallest <italic>P</italic>-value was selected as the primary trait in which replication was sought. Where multiple SNVs fitted these selection criteria for a single region, only the SNV with the smallest <italic>P</italic>-value was selected. In total, 81 SNVs were selected for validation in independent samples. These 81 SNVs had concordant association results for both transformed and non-transformed traits. Eighty SNVs were selected from EUR_SAS results (with consistent support in EUR), and one SNV from EUR results only. In the next step, we looked up the 81 SNV-BP associations using data from a separate consortium, the CHARGE+ exome chip blood pressure consortium (who had analysed untransformed SBP, DBP, PP and HTN), and UHP and Lolipop (ExomeBP consortium; <xref ref-type="supplementary-material" rid="SD4">Supplementary Tables 2 and 3</xref>). The analysed residuals from CHARGE+ were approximately normally distributed in their largest studies (<xref ref-type="supplementary-material" rid="SD1">Supplementary Figure 8</xref>).</p><p id="P42">Two meta-analyses of the replication datasets were performed: one of EUR samples, and a second of EUR, African American, Hispanics and SAS ancestries (“ALL”). Replication was confirmed if <italic>P</italic> (1-tailed) < 0.05/81=6.17x10<sup>-4</sup> and the effect (beta) was in the direction observed in discovery meta-analyses for the selected trait. A combined meta-analysis was performed of discovery (untransformed results as only untransformed data was available from CHARGE+ exome chip blood pressure consortium) and replication results across the four traits to assess the overall support for each locus. For the combined meta-analyses, a GWS threshold of, <italic>P</italic>≤5x10<sup>-8</sup>, was used to declare a SNV as novel rather than a less stringent experiment wide threshold, as GWS is used to declare significance in GWAS and we wish to minimise the possibility of false positive associations. (Note that GWS is equivalent to an exome-wide threshold of <italic>P</italic>≤2x10<sup>-7</sup> adjusted for four traits).</p><p id="P43">Note: all validated BP-associated variants were associated at <italic>P</italic><10<sup>-5</sup> in the discovery dataset (for the primary trait). Hence, we could have used the same inclusion criteria for both common and rare SNVs. Therefore the optimal threshold to choose for future experiments may need further consideration.</p></sec><sec id="S18"><title>Conditional analyses and gene-based tests</title><p id="P44">The RAREMETALWORKER (RMW) tool<xref rid="R15" ref-type="bibr">15</xref> (version 4.13.3) that does not require individual level data to perform conditional analyses and gene-based tests was used for conditional analyses. All studies that contributed to the SNV discovery analyses were re-contacted and asked to run RMW. Only FENLAND, GoDARTS, HELIC-MANOLIS, UKHLS and EPIC-InterAct were unable to run RMW, while two new studies were included, INCIPE and NFBC1966 (<xref ref-type="supplementary-material" rid="SD4">Supplementary Table 1 and 2</xref>). In total, 43 studies (147,402 samples) were included in the EUR analyses and 45 studies (173,329 samples) in the EUR_SAS analyses (<xref ref-type="supplementary-material" rid="SD4">Supplementary Tables 2 and 3</xref>). Comparison of discovery and RMW study level results were made (<xref ref-type="supplementary-material" rid="SD2">Supplementary Information</xref>).</p><p id="P45">For each novel locus, the genomic coordinates and size of the region were defined according to recombination rates (<xref ref-type="supplementary-material" rid="SD4">Supplementary Table 9</xref>) around the lead variant. For known loci, a 1 Mb window was used (<xref ref-type="supplementary-material" rid="SD4">Supplementary Table 14</xref>). Conditional analyses were performed across each region, in both EUR and EUR_SAS samples, for the transformed phenotype corresponding to the validated BP trait for novel loci and the published BP trait for known loci.</p><p id="P46">Gene based tests were performed in both the EUR and EUR_SAS datasets using the Sequence Kernel Association Test (SKAT)<xref rid="R16" ref-type="bibr">16</xref> method implemented in RMW as it allows for the SNVs to have different directions and magnitudes of effect. Burden tests were also performed but are not presented as only SKAT provided significant results. The variants in the gene-based tests using SKAT were weighted using the default settings, <italic>i.e.</italic> a beta distribution density function to up-weight rare variants, Beta(MAF<italic>j</italic>,1,25) where MAF<italic>j</italic> represents the pooled MAF for variant <italic>j</italic> across all studies. Analyses were restricted to coding SNVs with MAF<5% and <1%. Genes were deemed to be associated if <italic>P</italic> <2.8x10<sup>-6</sup> (Bonferroni adjusted for 17,996 genes). To confirm the gene associations were not attributable to a solitary SNV, a gene-based test conditional on the most associated SNV was performed (<italic>P</italic><sub>conditional</sub>< 0.001). The QC of all SNVs contributing to the gene based tests including the number of samples and studies were checked prior to claiming association. We sought replication of associated genes in the CHARGE+ exome chip blood pressure consortium.</p></sec><sec id="S19"><title>Pathway analyses with MAGENTA</title><p id="P47">We tested seven databases in MAGENTA<xref rid="R37" ref-type="bibr">37</xref> (BioCarta, Kyoto Encyclopedia of Genes and Genomes, Ingenuity, Panther, Panther Biological Processes, Panther Molecular Functions and Reactome) for overrepresentation of the SNV discovery results from both EUR and EUR_SAS ancestries. Each of the four BP phenotypes were tested. Pathways exhibiting <italic>P</italic><0.01 and FDR<5% were considered statistically significant.</p></sec><sec id="S20"><title>GeneGo MetaCore Network analyses</title><p id="P48">A set of BP genes based on previously published studies and our current results (locus defined as r<sup>2</sup>>0.4 and 500kb on either side of the lead SNV; <xref ref-type="supplementary-material" rid="SD4">Supplementary Table 19</xref>) were tested for enrichment using the THOMSON REUTERS MetaCore™ Single Experiment Analysis workflow tool. The data were mapped onto selected MetaCore ontology databases: pathway maps, process networks, GO processes and diseases / biomarkers, for which functional information is derived from experimental literature. Outputs were sorted based on <italic>P</italic>- and FDR-values. A gene set was considered enriched for a particular process if <italic>P</italic><0.05 and FDR<5%.</p></sec><sec id="S21"><title>Genetic Risk Score</title><p id="P49">To assess the effect of BP on CHD, ischemic stroke (and subtypes: large vessel, small vessel and cardioembolic stroke) left ventricular mass, left ventricular wall thickness, heart failure, HDL-c, LDL-c, total cholesterol, triglycerides and eGFR, we performed a weighted generalized linear regression of the genetic associations with each outcome variable on the genetic associations with BP.</p><p id="P50">When genetic variants are uncorrelated, the estimates from such a weighted linear regression analysis using summarized data, and a genetic risk score analysis using individual-level data, are equal<xref rid="R48" ref-type="bibr">48</xref>. We refer to the analysis as a genetic risk score (also known as a polygenic risk score) analysis as this is likely to be more familiar to applied readers. As some of the genetic variants in our analysis are correlated, a generalized weighted linear regression model is fitted that accounts for the correlations between variants, as follows: If <italic>β</italic><sub>X</sub> are the genetic associations (beta-coefficients) with the risk factor (here, BP) and <italic>β</italic><sub>Y</sub> are the genetic associations with the outcome, then the causal estimate from a weighted generalized linear regression is (<italic>β</italic><sub>X</sub><sup>T</sup><italic>Ώ</italic><sup>-1</sup><italic>β</italic><sub>X</sub>)<sup>-1</sup><italic>β</italic><sub>X</sub><sup>T</sup><italic>Ώ</italic><sup>-1</sup><italic>β</italic><sub>Y</sub>, with standard error, <disp-formula id="FD1"><mml:math display="block" id="M1" overflow="scroll"><mml:mrow><mml:mover accent="true"><mml:mi>σ</mml:mi><mml:mo>^</mml:mo></mml:mover><mml:msqrt><mml:mrow><mml:msup><mml:mrow><mml:mo stretchy="false">(</mml:mo><mml:mrow><mml:msup><mml:msub><mml:mrow><mml:mrow><mml:mi>β</mml:mi></mml:mrow></mml:mrow><mml:mrow><mml:mi>X</mml:mi></mml:mrow></mml:msub><mml:mi>T</mml:mi></mml:msup></mml:mrow><mml:msup><mml:mo>Ω</mml:mo><mml:mrow><mml:mo>−</mml:mo><mml:mn>1</mml:mn></mml:mrow></mml:msup><mml:msub><mml:mi>β</mml:mi><mml:mi>X</mml:mi></mml:msub><mml:mo stretchy="false">)</mml:mo></mml:mrow><mml:mrow><mml:mo>−</mml:mo><mml:mn>1</mml:mn></mml:mrow></mml:msup></mml:mrow></mml:msqrt><mml:mo>,</mml:mo></mml:mrow></mml:math></disp-formula> where <sup><italic>T</italic></sup> is a matrix transpose, <italic>σ̂</italic> is the estimate of the residual standard error from the regression model, and the weighting matrix <italic>Ώ</italic> has terms <disp-formula id="FD2"><mml:math display="block" id="M2" overflow="scroll"><mml:mrow><mml:msub><mml:mo>Ω</mml:mo><mml:mrow><mml:msub><mml:mi>j</mml:mi><mml:mn>1</mml:mn></mml:msub><mml:msub><mml:mi>j</mml:mi><mml:mn>2</mml:mn></mml:msub></mml:mrow></mml:msub><mml:mo>=</mml:mo><mml:msub><mml:mo>σ</mml:mo><mml:mrow><mml:mi>Y</mml:mi><mml:msub><mml:mi>j</mml:mi><mml:mn>1</mml:mn></mml:msub></mml:mrow></mml:msub><mml:msub><mml:mo>σ</mml:mo><mml:mrow><mml:mi>Y</mml:mi><mml:msub><mml:mi>j</mml:mi><mml:mn>2</mml:mn></mml:msub></mml:mrow></mml:msub><mml:msub><mml:mo>ρ</mml:mo><mml:mrow><mml:msub><mml:mi>j</mml:mi><mml:mn>1</mml:mn></mml:msub><mml:msub><mml:mi>j</mml:mi><mml:mn>2</mml:mn></mml:msub></mml:mrow></mml:msub></mml:mrow></mml:math></disp-formula>, where <italic>σ</italic><sub>Yj</sub> is the standard error of the genetic association with the outcome for the <italic>j</italic>th SNV, and <italic>ρ</italic><sub>j1j2</sub> is the correlation between the <italic>j<sub>1</sub></italic>th and <italic>j<sub>2</sub></italic> th SNVs. The presence of the estimated residual standard error allows for heterogeneity between the causal estimates from the individual SNVs as overdispersion in the regression model (in the case of underdispersion, the residual standard error estimate is set to unity). This is equivalent to combining the causal estimates from each SNV using a multiplicative random-effects model<xref rid="R49" ref-type="bibr">49</xref>.</p><p id="P51">For each of SBP, DBP and PP, the score was created using both the novel and known BP SNVs or a close proxy (r<sup>2</sup>>0.8). Both the sentinel SNV association and any secondary SNV associations that remained after adjusting for the sentinel SNV were included in the genetic risk score. For the 30 validated novel SNV-BP associations, βs were taken from the independent replication analyses (<xref ref-type="table" rid="T1">Table 1</xref> and <xref ref-type="table" rid="T2">2</xref>) to weight the SNV in the genetic risk score. For the secondary SNVs from the seven novel loci and five known loci, βs were taken from the discovery analyses (<xref ref-type="supplementary-material" rid="SD4">Supplementary Tables 10 and 15</xref>). For the 82 known SNVs, 43 were either genotyped or had proxies on the Exome chip and the βs were taken from discovery results (<xref ref-type="supplementary-material" rid="SD4">Supplementary Table 13</xref>), the remaining βs were taken from published effect estimates. This strategy for selecting betas for use in the GRS was taken to minimize the influence of winner’s curse. The associations between the BP variants with CHD, HDL-c, LDL-c, total cholesterol, log(triglycerides) and log(eGFR) were obtained using the CHD Exome+ Consortium studies, the associations with BMI, waist-hip ratio adjusted BMI and height from the GIANT consortium (unpublished data), ischemic stroke from METASTROKE<xref rid="R25" ref-type="bibr">25</xref>, and left ventricular mass, left ventricular wall thickness and heart failure from EchoGen<xref rid="R27" ref-type="bibr">27</xref> and CHARGE-HF<xref rid="R26" ref-type="bibr">26</xref>. A causal interpretation of the association of GRS with the outcome as the effect of BP on the outcome assumes that the effects of genetic variants on the outcome are mediated via blood pressure and not via alternate causal pathways, for example via LV thickness. There are also limitations of the Mendelian randomization approach in distinguishing between the causal effects of different measures of blood pressure, due to the paucity of genetic variants associated with only one measure of blood pressure.</p></sec><sec id="S22"><title>eQTL analyses</title><p id="P52">The MuTHER dataset contains gene expression data from 850 UK twins for 23,596 probes and 2,029,988 (HapMap 2 imputed) SNVs. All cis–associated SNVs with FDR<1%, within each of the 30 novel regions (IMPUTE info score >0.8) were extracted from the MuTHER project dataset for, LCL (n=777), adipose (n=776) and skin (n=667) <xref rid="R50" ref-type="bibr">50</xref>. The pilot phase of the GTEx Project (dbGaP Accession phs000424.v3.p1) provides expression data from up to 156 individuals for 52,576 genes and 6,820,472 genotyped SNVs (imputed to 1000 Genomes project, MAF≥5%)<xref rid="R51" ref-type="bibr">51</xref>. The eQTL analysis was focused on subcutaneous adipose tissue (n=94), tibial artery (n=112), heart (left ventricle) (n=83), lung (n=119), skeletal muscle (n=138), tibial nerve (n=88), skin (sun exposed, lower leg) (n=96), thyroid (n=105) and whole blood (n=156) which have >80 samples and genes expressed at least 0.1 RPKM in 10 or more individuals in a given tissue. All transcripts with a transcription start site (TSS) within one of the 30 new BP loci and for which there was a cis-associated SNV (IMPUTE info score >0.4) within 1Mb of the TSS at FDR<5%, were identified. Kidney was not evaluated because the sample size was too small (n=8). From each resource, we report eQTL signals, which reach the resource-specific thresholds for significance described above, for SNVs that are in LD (r<sup>2</sup>>0.8) with our sentinel SNV.</p><p id="P53">For identified eQTLs, we tested whether they colocalised with the BP associated SNV<xref rid="R52" ref-type="bibr">52</xref>. Colocalisation analyses were considered to be significant if the posterior probability of colocalisation was greater than 0.95.</p></sec><sec id="S23"><title>Annotation of variants</title><p id="P54"><italic>In silico</italic> prediction of the functional effect of associated variants was based on the annotation from dbSNP, the Ensembl Variant Effect Predictor tool and the Exome Variant Server, NHLBI GO Exome Sequencing Project (ESP), Seattle, WA.</p></sec><sec id="S24"><title>Trait variance explained</title><p id="P55">The percentage trait variance explained for SBP, DBP, PP was assessed with 5,861 individuals with complete information for all phenotypes and covariates from the population-based cohort, 1958BC.</p><p id="P56">Two genetic models were investigated: one containing the 43 previously known BP associated SNVs covered on the Exome chip; the other additionally including the 30 novel lead SNVs and 9 conditionally independent SNVs from both novel and known loci. These nine conditionally independent SNVs were taken from the EUR results, as 1958BC is EUR. They included four from novel loci (<italic>PREX1, COL21A1, PRKAG1</italic> and <italic>MYH6</italic> (there was only 1 in EUR); <xref ref-type="supplementary-material" rid="SD4">Supplementary Table 10</xref>) and five from known loci (<italic>ST7L-CAPZA1-MOV10, FIGN-GRB14, ENPEP, TBX5-TBX3</italic> and <italic>HOXC4</italic>; <xref ref-type="supplementary-material" rid="SD4">Supplementary Table 15</xref>).</p><p id="P57">The residual trait was obtained by adjusting each of the BP traits in a regression model with sex and BMI variables (not age or age<sup>2</sup> as all 1958BC individuals were aged 44 years). The residual trait was regressed on all SNVs within the corresponding model and adjusted for the first ten PCs. The R<sup>2</sup> calculated from this regression model was used as the percentage trait variance explained.</p></sec><sec id="S25"><title>Monogenic Enrichment analyses</title><p id="P58">To determine if sub-significant signals of association were present in a set of genes associated with monogenic forms of disease, we performed an enrichment analysis of the discovery single variant meta-analyses association results for all four traits, both for EUR and EUR_SAS datasets.</p><p id="P59">The monogenic gene set included: <italic>WNK1</italic>, <italic>WNK4</italic>, <italic>KLHL3</italic>, <italic>CUL3</italic>, <italic>PPARG</italic>, <italic>NR3C2</italic>, <italic>CYP11B1</italic>, <italic>CYP11B2</italic>, <italic>CYP17A1</italic>, <italic>HSD11B2</italic>, <italic>SCNN1A</italic>, <italic>SCNN1B</italic>, <italic>SCNN1G</italic>, <italic>CLCNKB</italic>, <italic>KCNJ1</italic>, <italic>SLC12A1</italic>, <italic>SLC12A3</italic><xref rid="R3" ref-type="bibr">3</xref>. The association results of coding SNVs in these genes were extracted and the number of tests with <italic>P</italic><0.001 observed. In order to determine how often such an observation would be observed by chance, we constructed 1,000 matched gene sets. The matching criteria for each monogenic gene was the intersection of all genes in the same exon length quintile and all genes in the same coding variant count decile. Within the matched sets, the number of variants with <italic>P</italic><0.001 was observed. The empirical <italic>P</italic>-value was calculated as the fraction of matched sets with an equal or larger number of variants less than 0.001.</p></sec></sec><sec sec-type="supplementary-material" id="SM"><title>Supplementary Material</title><supplementary-material content-type="local-data" id="SD1"><label>Supplementary Figures</label><media xlink:href="NIHMS69533-supplement-Supplementary_Figures.pdf" mimetype="application" mime-subtype="pdf" orientation="portrait" xlink:type="simple" id="d37e4575" position="anchor"></media></supplementary-material><supplementary-material content-type="local-data" id="SD2"><label>Supplementary Information</label><media xlink:href="NIHMS69533-supplement-Supplementary_Information.docx" mimetype="application" mime-subtype="octet-stream" orientation="portrait" xlink:type="simple" id="d37e4579" position="anchor"></media></supplementary-material><supplementary-material content-type="local-data" id="SD3"><label>Supplementary Information Titles</label><media xlink:href="NIHMS69533-supplement-Supplementary_Information_Titles.docx" mimetype="application" mime-subtype="octet-stream" orientation="portrait" xlink:type="simple" id="d37e4583" position="anchor"></media></supplementary-material><supplementary-material content-type="local-data" id="SD4"><label>Supplementary Tables</label><media xlink:href="NIHMS69533-supplement-Supplementary_Tables.xlsx" mimetype="application" mime-subtype="octet-stream" orientation="portrait" xlink:type="simple" id="d37e4587" position="anchor"></media></supplementary-material></sec></body><back><ack id="S26"><title>Acknowledgements</title><p>(See <xref ref-type="supplementary-material" rid="SD2">Supplementary information</xref>)</p></ack><fn-group><fn id="FN2"><p id="P60"><bold>URLs</bold></p><p id="P61">Exome chip design information: <ext-link ext-link-type="uri" xlink:href="http://genome.sph.umich.edu/wiki/Exome_Chip_Design">http://genome.sph.umich.edu/wiki/Exome_Chip_Design</ext-link></p><p id="P62">RareMetalWorker information: <ext-link ext-link-type="uri" xlink:href="http://genome.sph.umich.edu/wiki/RAREMETALWORKER">http://genome.sph.umich.edu/wiki/RAREMETALWORKER</ext-link></p><p id="P63">Summary SNV association results: <ext-link ext-link-type="uri" xlink:href="http://www.phenoscanner.medschl.cam.ac.uk">http://www.phenoscanner.medschl.cam.ac.uk</ext-link></p><p id="P64">Databases used for variant annotation: <ext-link ext-link-type="uri" xlink:href="http://www.ncbi.nlm.nih.gov/SNP/">http://www.ncbi.nlm.nih.gov/SNP/</ext-link><ext-link ext-link-type="uri" xlink:href="http://www.ensembl.org/info/docs/tools/index.html">http://www.ensembl.org/info/docs/tools/index.html</ext-link> and <ext-link ext-link-type="uri" xlink:href="http://evs.gs.washington.edu/EVS/">http://evs.gs.washington.edu/EVS/</ext-link></p><p id="P65">UCSC reference file used for annotation of variants with gene and exon information: <ext-link ext-link-type="uri" xlink:href="http://hgdownload.soe.ucsc.edu/goldenPath/hg19/database/refFlat.txt.gz">http://hgdownload.soe.ucsc.edu/goldenPath/hg19/database/refFlat.txt.gz</ext-link></p><p id="P66">Databases used for pathway analysis: MAGENTA (<ext-link ext-link-type="uri" xlink:href="https://www.broadinstitute.org/mpg/magenta/">https://www.broadinstitute.org/mpg/magenta/</ext-link>) and THOMSON REUTERS MetaCore™ Single Experiment Analysis workflow tool (<ext-link ext-link-type="uri" xlink:href="http://thomsonreuters.com/en/products-services/pharma-life-sciences/pharmaceutical-research/metacore.html">http://thomsonreuters.com/en/products-services/pharma-life-sciences/pharmaceutical-research/metacore.html</ext-link>).</p></fn><fn fn-type="con" id="FN3"><p id="P67"><bold>Author contributions</bold></p><p id="P68">Supervision and management of the project: JMHH and PBM. The following authors contributed to the drafting of the manuscript: JMMH, PBM, PSu, HW, ASB, FD, JPC, DRB, KW, MT, FWA, LVW, NJS, JD AKM, HY, CMM, NG, XS, TaT, DFF, MHs, OG, TF, VT. All authors critically reviewed and approved the final version of the manuscript. <bold>Statistical analysis review:</bold> JMMH, PSu, FD, HW, JPC, RY, NM, PBM, LVW, HY, TF, EMi, ADM, AM, AM, EE, ASB, FWA, MJC, CF, TF, SEH, ASH, JEH, JL, GM, JM, NM, APM, APo, NJS, RAS, LS, KE, MT, VT, TVV, NV, KW, AMY, WZg, NG, CML, AKM, XS, TT. <bold>Central Data QC</bold>: JMMH, ASB, PSu, RY, FD, HW, JPC, TF, LVW, PBM, EMi, NM, CML, NG, XS, AKM. <bold>Central Data analysis:</bold> JMMH, PSu, FD, HW, JPC, NG, CML, AKM, XS. <bold>Pathway analysis and literature review:</bold> JMMH, DRB, PBM, MT, KW, VT, OG, AT, FWA. <bold>GWAS lookups, eQTL analysis, GRS, variant annotation and enrichment analyses:</bold> JMMH, ASB, DRB, JRS, DFF, FD, MHr, PBM, FWA, TT, CML, AKM, SBu. <bold>Study Investigators in alphabetical order by consortium (CHD Exome+, ExomeBP and GoT2D)</bold>: DSA, PA, EA, DA, ASB, RC, JD, JF, IF, PF, JWJ, FKe, ASM, SFN, BGN, DS, NSa, JV, FWA, PIWB, MJB, MJC, JCC, JMC, IJD, GD, AFD, PE, TE, PWF, GG, PH, CH, KH, EI, MJ, FKa, SK, JSK, LLi, MIM, OM, AMe, ADM, APM, PBM, MEN, SP, CP, OPo, DP, SR, OR, IR, VS, NJS, PSe, TDS, JMS, NJW, CJW, EZ, MB, IB, FSC, LG, TH, EKH, PJ, JKu, ML, TAL, AL, KLM, HO, OPe, RR, JT, MU. <bold>Study Phenotyping in alphabetical order by consortium (CHD Exome+, ExomeBP and GoT2D)</bold>: PA, DA, SBl, MC, JF, JWJ, FKe, KK, SFN, BGN, CJP, AR, MS, NSa, JV, WZo, RAB, MJB, MJC, JCC, JMC, AFD, ASFD, LAD, TE, AF, GG, GH, PH, AS H, OLH, EI, MJ, FK, JSK, LLi, LLa, GM, AMc, PM, AMe, RMg, MJN, MEN, OPo, NP, FR, VS, NJS, TDS, AVS, JMS, MT, AV, NV, NJW, TiT, CC, LLH, MEJ, AK, PK, JL DPS, SM, ERBP, AS, TS, HMS, BT. <bold>Study Data QC and analysis in alphabetical order by consortium (CHD Exome+, ExomeBP and GoT2D):</bold> ASB, AJMC, JMMH, JK, SFN, BGN, MMN, SP, MP, PSu, ST, GV, SMW, RY, FWA, JPC, FD, AF, TF, CH, AMc, AMj, APM, PBM, CP, WR, FR, NJS, MT, VT, HW, HY, NG, AKM, XS. <bold>Exome chip data QC in alphabetical order by consortium (CHD Exome+, ExomeBP and GoT2D)</bold>: ASB, JMMH, SFN, BGN, PSu, RY, FWA, PIWB, AIFB, JCC, JPC, PD, LAD, FD, EE, CF, TF, SEH, PH, SSH, KH, JEH, EK, AMj, GM, JM, NM, EMi, AMo, APM, PBM, CPN, MJN, CP, AP, WR, NRR, RAS, NS, LS, KES, MDT, VT, TVV, TVV, NV, HW, HY, AMY, EZ, WZg, NG, CML, AKM, XS. <bold>Exome chip Data analysis in alphabetical order by consortium (CHD Exome+, ExomeBP and GoT2D):</bold> JMMH, PSu, RY, FWA, PIWB, AIFB, RAB, MJC, JCC, JPC, PD, LAD, PE, EE, CF, TF, PWF, SF, CG, SEH, PH, ASH, CH, OLH, JEH, EI, MJ, FKa, JSK, DCML, LLi, JL, GM, RMr, JM, NM, MIM, PM, OM, CM, EMi, AMo, APM, RMg, PBM, CPN, MJN, TO, APo, APa, WR, NRR, NJS, RAS, NS, LS, TDS, KES, MDT, ET, VT, TVV, NV, LVW, NJW, HW, HY, AMY, EZ, HZ, WZg, LLB, APG, NG, MHs, JRH, AUJ, JBJ, CML, AKM, NN, XS, AS, AJS. <bold>GRS lookups:</bold> AEJ, EMa, HFM, HL, HMH, JFF, MTr, RSV, WL.</p></fn><fn fn-type="COI-statement" id="FN4"><p id="P69"><bold>Conflict of interests</bold></p><p id="P70">N. P. has received financial support from several pharmaceutical companies that manufacture either blood pressure lowering or lipid lowering agents, or both, and consultancy fees.</p><p id="P71">S. K. has received Research Grant-Merck, Bayer, Aegerion; SAB-Catabasis, Regeneron Genetics Center, Merck, Celera; Equity-San Therapeutics, Catabasis; Consulting-Novartis, Aegerion, Bristol Myers-Squibb, Sanofi, AstraZeneca, Alnylam.</p><p id="P72">P. Sever has received research awards from Pfizer Inc.</p><p id="P73">A. Malarstig and M. Uria-Nickelsen are full time employees of Pfizer.</p><p id="P74">D. Reily and M. Hoek are full time employees of Merck and co Inc.</p><p id="P75">M.J. Caulfield is Chief Scientist for Genomics England a UK Government company.</p><p id="P76">The authors declare no competing financial interest.</p></fn></fn-group><ref-list><ref id="R1"><label>1</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lim</surname><given-names>SS</given-names></name><etal></etal></person-group><article-title>A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010</article-title><source>Lancet</source><year>2012</year><volume>380</volume><fpage>2224</fpage><lpage>60</lpage><pub-id pub-id-type="pmid">23245609</pub-id></element-citation></ref><ref id="R2"><label>2</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Rapsomaniki</surname><given-names>E</given-names></name><etal></etal></person-group><article-title>Blood pressure and incidence of twelve cardiovascular diseases: lifetime risks, healthy life-years lost, and age-specific associations in 1.25 million people</article-title><source>Lancet</source><year>2014</year><volume>383</volume><fpage>1899</fpage><lpage>911</lpage><pub-id pub-id-type="pmid">24881994</pub-id></element-citation></ref><ref id="R3"><label>3</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Munroe</surname><given-names>PB</given-names></name><name><surname>Barnes</surname><given-names>MR</given-names></name><name><surname>Caulfield</surname><given-names>MJ</given-names></name></person-group><article-title>Advances in blood pressure genomics</article-title><source>Circ Res</source><year>2013</year><volume>112</volume><fpage>1365</fpage><lpage>79</lpage><pub-id pub-id-type="pmid">23661711</pub-id></element-citation></ref><ref id="R4"><label>4</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ehret</surname><given-names>GB</given-names></name><etal></etal></person-group><article-title>Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk</article-title><source>Nature</source><year>2011</year><volume>478</volume><fpage>103</fpage><lpage>109</lpage><pub-id pub-id-type="pmid">21909115</pub-id></element-citation></ref><ref id="R5"><label>5</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wain</surname><given-names>LV</given-names></name><etal></etal></person-group><article-title>Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure</article-title><source>Nature Genetics</source><year>2011</year></element-citation></ref><ref id="R6"><label>6</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Johnson</surname><given-names>T</given-names></name><etal></etal></person-group><article-title>Blood pressure loci identified with a gene-centric array</article-title><source>Am J Hum Genet</source><year>2011</year><volume>89</volume><fpage>688</fpage><lpage>700</lpage><pub-id pub-id-type="pmid">22100073</pub-id></element-citation></ref><ref id="R7"><label>7</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tomaszewski</surname><given-names>M</given-names></name><etal></etal></person-group><article-title>Genetic architecture of ambulatory blood pressure in the general population: insights from cardiovascular gene-centric array</article-title><source>Hypertension</source><year>2010</year><volume>56</volume><fpage>1069</fpage><lpage>76</lpage><pub-id pub-id-type="pmid">21060006</pub-id></element-citation></ref><ref id="R8"><label>8</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tragante</surname><given-names>V</given-names></name><etal></etal></person-group><article-title>Gene-centric meta-analysis in 87,736 individuals of European ancestry identifies multiple blood-pressure-related loci</article-title><source>Am J Hum Genet</source><year>2014</year><volume>94</volume><fpage>349</fpage><lpage>60</lpage><pub-id pub-id-type="pmid">24560520</pub-id></element-citation></ref><ref id="R9"><label>9</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ganesh</surname><given-names>SK</given-names></name><etal></etal></person-group><article-title>Loci influencing blood pressure identified using a cardiovascular gene-centric array</article-title><source>Hum Mol Genet</source><year>2013</year></element-citation></ref><ref id="R10"><label>10</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Simino</surname><given-names>J</given-names></name><etal></etal></person-group><article-title>Gene-age interactions in blood pressure regulation: a large-scale investigation with the CHARGE, Global BPgen, and ICBP Consortia</article-title><source>Am J Hum Genet</source><year>2014</year><volume>95</volume><fpage>24</fpage><lpage>38</lpage><pub-id pub-id-type="pmid">24954895</pub-id></element-citation></ref><ref id="R11"><label>11</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zhu</surname><given-names>X</given-names></name><etal></etal></person-group><article-title>Meta-analysis of Correlated Traits via Summary Statistics from GWASs with an Application in Hypertension</article-title><source>Am J Hum Genet</source><year>2015</year><volume>96</volume><fpage>21</fpage><lpage>36</lpage><pub-id pub-id-type="pmid">25500260</pub-id></element-citation></ref><ref id="R12"><label>12</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Salfati</surname><given-names>E</given-names></name><name><surname>Morrison</surname><given-names>AC</given-names></name><name><surname>Boerwinkle</surname><given-names>E</given-names></name><name><surname>Chakravarti</surname><given-names>A</given-names></name></person-group><article-title>Direct Estimates of the Genomic Contributions to Blood Pressure Heritability within a Population-Based Cohort (ARIC)</article-title><source>PLoS One</source><year>2015</year><volume>10</volume><fpage>e0133031</fpage><pub-id pub-id-type="pmid">26162070</pub-id></element-citation></ref><ref id="R13"><label>13</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Schork</surname><given-names>NJ</given-names></name><name><surname>Murray</surname><given-names>SS</given-names></name><name><surname>Frazer</surname><given-names>KA</given-names></name><name><surname>Topol</surname><given-names>EJ</given-names></name></person-group><article-title>Common vs. rare allele hypotheses for complex diseases</article-title><source>Curr Opin Genet Dev</source><year>2009</year><volume>19</volume><fpage>212</fpage><lpage>9</lpage><pub-id pub-id-type="pmid">19481926</pub-id></element-citation></ref><ref id="R14"><label>14</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Nejentsev</surname><given-names>S</given-names></name><name><surname>Walker</surname><given-names>N</given-names></name><name><surname>Riches</surname><given-names>D</given-names></name><name><surname>Egholm</surname><given-names>M</given-names></name><name><surname>Todd</surname><given-names>JA</given-names></name></person-group><article-title>Rare variants of IFIH1, a gene implicated in antiviral responses, protect against type 1 diabetes</article-title><source>Science</source><year>2009</year><volume>324</volume><fpage>387</fpage><lpage>9</lpage><pub-id pub-id-type="pmid">19264985</pub-id></element-citation></ref><ref id="R15"><label>15</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Liu</surname><given-names>DJ</given-names></name><etal></etal></person-group><article-title>Meta-analysis of gene-level tests for rare variant association</article-title><source>Nat Genet</source><year>2014</year><volume>46</volume><fpage>200</fpage><lpage>4</lpage><pub-id pub-id-type="pmid">24336170</pub-id></element-citation></ref><ref id="R16"><label>16</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wu</surname><given-names>MC</given-names></name><etal></etal></person-group><article-title>Rare-variant association testing for sequencing data with the sequence kernel association test</article-title><source>Am J Hum Genet</source><year>2011</year><volume>89</volume><fpage>82</fpage><lpage>93</lpage><pub-id pub-id-type="pmid">21737059</pub-id></element-citation></ref><ref id="R17"><label>17</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Li</surname><given-names>B</given-names></name><name><surname>Leal</surname><given-names>SM</given-names></name></person-group><article-title>Methods for detecting associations with rare variants for common diseases: application to analysis of sequence data</article-title><source>Am J Hum Genet</source><year>2008</year><volume>83</volume><fpage>311</fpage><lpage>21</lpage><pub-id pub-id-type="pmid">18691683</pub-id></element-citation></ref><ref id="R18"><label>18</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Vissers</surname><given-names>LE</given-names></name><etal></etal></person-group><article-title>Heterozygous germline mutations in A2ML1 are associated with a disorder clinically related to Noonan syndrome</article-title><source>Eur J Hum Genet</source><year>2015</year><volume>23</volume><fpage>317</fpage><lpage>24</lpage><pub-id pub-id-type="pmid">24939586</pub-id></element-citation></ref><ref id="R19"><label>19</label><element-citation publication-type="journal"><collab>International Consortium for Blood Pressure Genome-Wide Association, S</collab><etal></etal><article-title>Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk</article-title><source>Nature</source><year>2011</year><volume>478</volume><fpage>103</fpage><lpage>9</lpage><pub-id pub-id-type="pmid">21909115</pub-id></element-citation></ref><ref id="R20"><label>20</label><element-citation publication-type="journal"><person-group person-group-type="author"><collab>Coronary Artery Disease Genetics Consortium C4D</collab></person-group><article-title>A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease</article-title><source>Nat Genet</source><year>2011</year><volume>43</volume><fpage>339</fpage><lpage>44</lpage><pub-id pub-id-type="pmid">21378988</pub-id></element-citation></ref><ref id="R21"><label>21</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Schunkert</surname><given-names>H</given-names></name><etal></etal></person-group><article-title>Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease</article-title><source>Nat Genet</source><year>2011</year><volume>43</volume><fpage>333</fpage><lpage>8</lpage><pub-id pub-id-type="pmid">21378990</pub-id></element-citation></ref><ref id="R22"><label>22</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Arking</surname><given-names>DE</given-names></name><etal></etal></person-group><article-title>Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization</article-title><source>Nat Genet</source><year>2014</year><volume>46</volume><fpage>826</fpage><lpage>36</lpage><pub-id pub-id-type="pmid">24952745</pub-id></element-citation></ref><ref id="R23"><label>23</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>den Hoed</surname><given-names>M</given-names></name><etal></etal></person-group><article-title>Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders</article-title><source>Nat Genet</source><year>2013</year><volume>45</volume><fpage>621</fpage><lpage>31</lpage><pub-id pub-id-type="pmid">23583979</pub-id></element-citation></ref><ref id="R24"><label>24</label><element-citation publication-type="journal"><person-group person-group-type="author"><collab>Global Lipids Genetics Consortium</collab><etal></etal></person-group><article-title>Discovery and refinement of loci associated with lipid levels</article-title><source>Nat Genet</source><year>2013</year><volume>45</volume><fpage>1274</fpage><lpage>83</lpage><pub-id pub-id-type="pmid">24097068</pub-id></element-citation></ref><ref id="R25"><label>25</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Traylor</surname><given-names>M</given-names></name><etal></etal></person-group><article-title>Genetic risk factors for ischaemic stroke and its subtypes (the METASTROKE collaboration): a meta-analysis of genome-wide association studies</article-title><source>Lancet Neurol</source><year>2012</year><volume>11</volume><fpage>951</fpage><lpage>62</lpage><pub-id pub-id-type="pmid">23041239</pub-id></element-citation></ref><ref id="R26"><label>26</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Smith</surname><given-names>NL</given-names></name><etal></etal></person-group><article-title>Association of genome-wide variation with the risk of incident heart failure in adults of European and African ancestry: a prospective meta-analysis from the cohorts for heart and aging research in genomic epidemiology (CHARGE) consortium</article-title><source>Circ Cardiovasc Genet</source><year>2010</year><volume>3</volume><fpage>256</fpage><lpage>66</lpage><pub-id pub-id-type="pmid">20445134</pub-id></element-citation></ref><ref id="R27"><label>27</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Vasan</surname><given-names>RS</given-names></name><etal></etal></person-group><article-title>Genetic variants associated with cardiac structure and function: a meta-analysis and replication of genome-wide association data</article-title><source>JAMA</source><year>2009</year><volume>302</volume><fpage>168</fpage><lpage>78</lpage><pub-id pub-id-type="pmid">19584346</pub-id></element-citation></ref><ref id="R28"><label>28</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ehret</surname><given-names>GB</given-names></name><etal></etal></person-group><article-title>Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk</article-title><source>Nature</source><year>2011</year><volume>478</volume><fpage>103</fpage><lpage>109</lpage><pub-id pub-id-type="pmid">21909115</pub-id></element-citation></ref><ref id="R29"><label>29</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Russo</surname><given-names>SB</given-names></name><etal></etal></person-group><article-title>Ceramide synthase 5 mediates lipid-induced autophagy and hypertrophy in cardiomyocytes</article-title><source>J Clin Invest</source><year>2012</year><volume>122</volume><fpage>3919</fpage><lpage>30</lpage><pub-id pub-id-type="pmid">23023704</pub-id></element-citation></ref><ref id="R30"><label>30</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Oudot-Mellakh</surname><given-names>T</given-names></name><etal></etal></person-group><article-title>Genome wide association study for plasma levels of natural anticoagulant inhibitors and protein C anticoagulant pathway: the MARTHA project</article-title><source>Br J Haematol</source><year>2012</year><volume>157</volume><fpage>230</fpage><lpage>9</lpage><pub-id pub-id-type="pmid">22443383</pub-id></element-citation></ref><ref id="R31"><label>31</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Smith</surname><given-names>NL</given-names></name><etal></etal></person-group><article-title>Novel associations of multiple genetic loci with plasma levels of factor VII, factor VIII, and von Willebrand factor: The CHARGE (Cohorts for Heart and Aging Research in Genome Epidemiology) Consortium</article-title><source>Circulation</source><year>2010</year><volume>121</volume><fpage>1382</fpage><lpage>92</lpage><pub-id pub-id-type="pmid">20231535</pub-id></element-citation></ref><ref id="R32"><label>32</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bleil</surname><given-names>ME</given-names></name><name><surname>Gregorich</surname><given-names>SE</given-names></name><name><surname>McConnell</surname><given-names>D</given-names></name><name><surname>Rosen</surname><given-names>MP</given-names></name><name><surname>Cedars</surname><given-names>MI</given-names></name></person-group><article-title>Does accelerated reproductive aging underlie premenopausal risk for cardiovascular disease?</article-title><source>Menopause</source><year>2013</year><volume>20</volume><fpage>1139</fpage><lpage>46</lpage><pub-id pub-id-type="pmid">23591257</pub-id></element-citation></ref><ref id="R33"><label>33</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Guan</surname><given-names>R</given-names></name><etal></etal></person-group><article-title>rbm47, a novel RNA binding protein, regulates zebrafish head development</article-title><source>Dev Dyn</source><year>2013</year><volume>242</volume><fpage>1395</fpage><lpage>404</lpage><pub-id pub-id-type="pmid">24038582</pub-id></element-citation></ref><ref id="R34"><label>34</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wozniak</surname><given-names>MA</given-names></name><name><surname>Kwong</surname><given-names>L</given-names></name><name><surname>Chodniewicz</surname><given-names>D</given-names></name><name><surname>Klemke</surname><given-names>RL</given-names></name><name><surname>Keely</surname><given-names>PJ</given-names></name></person-group><article-title>R-Ras controls membrane protrusion and cell migration through the spatial regulation of Rac and Rho</article-title><source>Mol Biol Cell</source><year>2005</year><volume>16</volume><fpage>84</fpage><lpage>96</lpage><pub-id pub-id-type="pmid">15525681</pub-id></element-citation></ref><ref id="R35"><label>35</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tuckwell</surname><given-names>D</given-names></name></person-group><article-title>Identification and analysis of collagen alpha 1(XXI), a novel member of the FACIT collagen family</article-title><source>Matrix Biol</source><year>2002</year><volume>21</volume><fpage>63</fpage><lpage>6</lpage><pub-id pub-id-type="pmid">11827793</pub-id></element-citation></ref><ref id="R36"><label>36</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Huang</surname><given-names>J</given-names></name><etal></etal></person-group><article-title>Improved imputation of low-frequency and rare variants using the UK10K haplotype reference panel</article-title><source>Nat Commun</source><year>2015</year><volume>6</volume><fpage>8111</fpage><pub-id pub-id-type="pmid">26368830</pub-id></element-citation></ref><ref id="R37"><label>37</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Segre</surname><given-names>AV</given-names></name><etal></etal></person-group><article-title>Common inherited variation in mitochondrial genes is not enriched for associations with type 2 diabetes or related glycemic traits</article-title><source>PLoS Genet</source><year>2010</year><volume>6</volume></element-citation></ref><ref id="R38"><label>38</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Huan</surname><given-names>T</given-names></name><etal></etal></person-group><article-title>Integrative network analysis reveals molecular mechanisms of blood pressure regulation</article-title><source>Mol Syst Biol</source><year>2015</year><volume>11</volume><fpage>799</fpage></element-citation></ref><ref id="R39"><label>39</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Locke</surname><given-names>AE</given-names></name><etal></etal></person-group><article-title>Genetic studies of body mass index yield new insights for obesity biology</article-title><source>Nature</source><year>2015</year><volume>518</volume><fpage>197</fpage><lpage>206</lpage><pub-id pub-id-type="pmid">25673413</pub-id></element-citation></ref><ref id="R40"><label>40</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wood</surname><given-names>AR</given-names></name><etal></etal></person-group><article-title>Defining the role of common variation in the genomic and biological architecture of adult human height</article-title><source>Nat Genet</source><year>2014</year><volume>46</volume><fpage>1173</fpage><lpage>86</lpage><pub-id pub-id-type="pmid">25282103</pub-id></element-citation></ref><ref id="R41"><label>41</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Park</surname><given-names>HW</given-names></name><etal></etal></person-group><article-title>Serine-threonine kinase with-no-lysine 4 (WNK4) controls blood pressure via transient receptor potential canonical 3 (TRPC3) in the vasculature</article-title><source>Proc Natl Acad Sci U S A</source><year>2011</year><volume>108</volume><fpage>10750</fpage><lpage>5</lpage><pub-id pub-id-type="pmid">21670282</pub-id></element-citation></ref><ref id="R42"><label>42</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sudlow</surname><given-names>C</given-names></name><etal></etal></person-group><article-title>UK biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age</article-title><source>PLoS Med</source><year>2015</year><volume>12</volume><fpage>e1001779</fpage><pub-id pub-id-type="pmid">25826379</pub-id></element-citation></ref><ref id="R43"><label>43</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Te Riet</surname><given-names>L</given-names></name><name><surname>van Esch</surname><given-names>JH</given-names></name><name><surname>Roks</surname><given-names>AJ</given-names></name><name><surname>van den Meiracker</surname><given-names>AH</given-names></name><name><surname>Danser</surname><given-names>AH</given-names></name></person-group><article-title>Hypertension: Renin-Angiotensin-aldosterone system alterations</article-title><source>Circ Res</source><year>2015</year><volume>116</volume><fpage>960</fpage><lpage>75</lpage><pub-id pub-id-type="pmid">25767283</pub-id></element-citation></ref><ref id="R44"><label>44</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gao</surname><given-names>J</given-names></name><etal></etal></person-group><article-title>A new strategy for treating hypertension by blocking the activity of the brain renin-angiotensin system with aminopeptidase A inhibitors</article-title><source>Clin Sci (Lond)</source><year>2014</year><volume>127</volume><fpage>135</fpage><lpage>48</lpage><pub-id pub-id-type="pmid">24697296</pub-id></element-citation></ref><ref id="R45"><label>45</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tobin</surname><given-names>MD</given-names></name><name><surname>Sheehan</surname><given-names>NA</given-names></name><name><surname>Scurrah</surname><given-names>KJ</given-names></name><name><surname>Burton</surname><given-names>PR</given-names></name></person-group><article-title>Adjusting for treatment effects in studies of quantitative traits: antihypertensive therapy and systolic blood pressure</article-title><source>Stat Med</source><year>2005</year><volume>24</volume><fpage>2911</fpage><lpage>35</lpage><pub-id pub-id-type="pmid">16152135</pub-id></element-citation></ref><ref id="R46"><label>46</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mahajan</surname><given-names>A</given-names></name><etal></etal></person-group><article-title>Identification and Functional Characterization of G6PC2 Coding Variants Influencing Glycemic Traits Define an Effector Transcript at the G6PC2-ABCB11 Locus</article-title><source>PLoS Genet</source><year>2015</year><volume>11</volume><fpage>e1004876</fpage><pub-id pub-id-type="pmid">25625282</pub-id></element-citation></ref><ref id="R47"><label>47</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Willer</surname><given-names>CJ</given-names></name><name><surname>Li</surname><given-names>Y</given-names></name><name><surname>Abecasis</surname><given-names>GR</given-names></name></person-group><article-title>METAL: fast and efficient meta-analysis of genomewide association scans</article-title><source>Bioinformatics</source><year>2010</year><volume>26</volume><fpage>2190</fpage><lpage>1</lpage><pub-id pub-id-type="pmid">20616382</pub-id></element-citation></ref><ref id="R48"><label>48</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Burgess</surname><given-names>S</given-names></name><name><surname>Thompson</surname><given-names>SG</given-names></name></person-group><article-title>Multivariable Mendelian randomization: the use of pleiotropic genetic variants to estimate causal effects</article-title><source>Am J Epidemiol</source><year>2015</year><volume>181</volume><fpage>251</fpage><lpage>60</lpage><pub-id pub-id-type="pmid">25632051</pub-id></element-citation></ref><ref id="R49"><label>49</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Thompson</surname><given-names>SG</given-names></name><name><surname>Sharp</surname><given-names>SJ</given-names></name></person-group><article-title>Explaining heterogeneity in meta-analysis: a comparison of methods</article-title><source>Stat Med</source><year>1999</year><volume>18</volume><fpage>2693</fpage><lpage>708</lpage><pub-id pub-id-type="pmid">10521860</pub-id></element-citation></ref><ref id="R50"><label>50</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Nica</surname><given-names>AC</given-names></name><etal></etal></person-group><article-title>The architecture of gene regulatory variation across multiple human tissues: the MuTHER study</article-title><source>PLoS Genet</source><year>2011</year><volume>7</volume><fpage>e1002003</fpage><pub-id pub-id-type="pmid">21304890</pub-id></element-citation></ref><ref id="R51"><label>51</label><element-citation publication-type="journal"><collab>GTEx, Consortium</collab><article-title>Human genomics. The Genotype-Tissue Expression (GTEx) pilot analysis: multitissue gene regulation in humans</article-title><source>Science</source><year>2015</year><volume>348</volume><fpage>648</fpage><lpage>60</lpage><pub-id pub-id-type="pmid">25954001</pub-id></element-citation></ref><ref id="R52"><label>52</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Giambartolomei</surname><given-names>C</given-names></name><etal></etal></person-group><article-title>Bayesian test for colocalisation between pairs of genetic association studies using summary statistics</article-title><source>PLoS Genet</source><year>2014</year><volume>10</volume><fpage>e1004383</fpage><pub-id pub-id-type="pmid">24830394</pub-id></element-citation></ref></ref-list></back><floats-group><fig id="F1" orientation="portrait" position="float"><label>Figure 1</label><caption><title>Study design and work flow diagram of single variant discovery analyses.</title><p>EUR=European, SAS=South Asian, HIS=Hispanic, AA=African American, HTN=hypertension, BP=blood pressure, SBP=systolic blood pressure, DBP= diastolic blood pressure, PP=pulse pressure, N=sample size, MAF=minor allele frequency, <italic>P</italic>=<italic>P</italic>-value significance threshold, SNV=single-nucleotide variant, GWS=genome-wide significance *Further details of the selection criteria are provided in the <xref ref-type="sec" rid="S11">methods</xref>.</p></caption><graphic xlink:href="emss-69533-f001"></graphic></fig><fig id="F2" orientation="portrait" position="float"><label>Figure 2</label><caption><title>Overlap of the 30 novel loci associations across SBP, DBP, PP and HTN.</title><p>The Venn diagram shows which of the 30 newly identified BP loci are associated with multiple BP traits. Only SNV-BP trait associations that were genome-wide significant (<italic>P</italic> < 5x10<sup>-8</sup>) in the combined discovery and replication meta-analyses are listed for any given BP trait, within the corresponding ancestry dataset that the given locus was validated for (see <xref ref-type="table" rid="T1">Tables 1</xref> and <xref ref-type="table" rid="T2">2</xref>). The association of <italic>RRAS</italic> variant with SBP was replicated in the independent samples, but did not achieve GWS in the combined discovery and replication meta-analysis and is therefore only included for SBP. HTN=hypertension, SBP=systolic blood pressure, DBP= diastolic blood pressure, PP=pulse pressure.</p></caption><graphic xlink:href="emss-69533-f002"></graphic></fig><fig id="F3" orientation="portrait" position="float"><label>Figure 3</label><caption><title>Study design for conditional analyses and rare variant gene-based discovery analyses.</title><p>RMW=RareMetalWorker, EUR=European, SAS = South Asian, HTN=hypertension, BP=blood pressure, SBP=systolic blood pressure, DBP= diastolic blood pressure, PP=pulse pressure. N=sample size, MAF=minor allele frequency, <italic>P</italic>=<italic>P</italic>-value significance threshold, <italic>P</italic><sub>cond</sub>=conditional <italic>P</italic>-value significance threshold</p></caption><graphic xlink:href="emss-69533-f003"></graphic></fig><fig id="F4" orientation="portrait" position="float"><label>Figure 4</label><caption><title>Locus plot for <italic>A2ML1</italic> and secondary amino acid structure of the gene product.</title><p>(a) Locus plot for <italic>A2ML1</italic> associated with HTN identified through gene based tests. The variants’ positions along the gene (x axis, based on human genome build 37) and the –log<sub>10</sub>(<italic>P</italic>-value of association) (y axis) are indicated. The variants are colour coded: nonsense (black), missense, predicted damaging (blue), and missense (orange). The schematic above the x-axis represents the intron / exon (black vertical bars) structure, the untranslated regions are shown as grey vertical bars.</p><p>(b) The white box denotes the full-length amino acid sequence for each of the two gene products. Black numbers denote amino acid residue positions of note. Coloured boxes depict putative functional domains (see below). Coloured vertical lines indicate the amino acid substitutions corresponding to the variants depicted in the locus plots above using the same colour coding. Bold, italic indicates the SNV association with smallest <italic>P</italic>-value.</p><p>Dark grey – signal peptide sequence. Brown – regions of intramolecular disulfide bonds. For simplicity only those regions coinciding with variants described were indicated. Black – bait region described to interact with proteases. Purple – thiol ester sequence region aiding in interaction with proteases. Light grey – alpha helical regions thought to mediate A2ML1 interaction with LRP1, facilitating receptor-mediated endocytosis.</p></caption><graphic xlink:href="emss-69533-f004"></graphic></fig><table-wrap id="T1" position="float" orientation="portrait"><label>Table 1</label><caption><title>Novel blood pressure trait associated loci. Variants with formal replication</title></caption><table frame="hsides" rules="groups"><thead><tr><th align="center" colspan="3" valign="top" rowspan="1">Variant information</th><th align="center" rowspan="1" colspan="1"></th><th align="center" colspan="2" valign="top" rowspan="1">Discovery<hr></hr></th><th align="center" colspan="3" valign="top" rowspan="1">Replication</th><th align="center" colspan="3" valign="top" rowspan="1">Combined<hr></hr></th></tr><tr><th align="center" valign="top" rowspan="1" colspan="1">Locus</th><th align="center" valign="top" rowspan="1" colspan="1">rsID</th><th align="left" valign="top" rowspan="1" colspan="1">Chr:Pos (EA:EAF)</th><th align="center" valign="top" rowspan="1" colspan="1">Trait</th><th align="center" valign="top" rowspan="1" colspan="1">P<sub>t</sub></th><th align="center" valign="top" rowspan="1" colspan="1"><italic>P<sub>U</sub></italic></th><th align="center" valign="top" rowspan="1" colspan="1">N</th><th align="center" valign="top" rowspan="1" colspan="1">β</th><th align="center" valign="top" rowspan="1" colspan="1"><italic>P</italic></th><th align="center" valign="top" rowspan="1" colspan="1">N</th><th align="center" valign="top" rowspan="1" colspan="1">β</th><th align="center" valign="top" rowspan="1" colspan="1"><italic>P</italic></th></tr></thead><tbody><tr><td align="left" colspan="12" valign="top" rowspan="1"><bold>EUR</bold></td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"><italic>RNF207</italic></td><td align="center" valign="top" rowspan="1" colspan="1">rs709209</td><td align="left" valign="top" rowspan="1" colspan="1">1:6.28 (A:0.655)</td><td align="center" valign="top" rowspan="1" colspan="1">PP</td><td align="center" valign="top" rowspan="1" colspan="1">4.57 x 10<sup>-6</sup></td><td align="center" valign="top" rowspan="1" colspan="1">1.60 x 10<sup>-6</sup></td><td align="center" valign="top" rowspan="1" colspan="1">122,780</td><td align="center" valign="top" rowspan="1" colspan="1">0.17</td><td align="center" valign="top" rowspan="1" colspan="1">5.83 x 10<sup>-4</sup></td><td align="center" valign="top" rowspan="1" colspan="1">284,683</td><td align="center" valign="top" rowspan="1" colspan="1">0.20</td><td align="center" valign="top" rowspan="1" colspan="1">9.62 x 10<sup>-9</sup></td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"><italic>C5orf56</italic></td><td align="center" valign="top" rowspan="1" colspan="1">rs12521868</td><td align="left" valign="top" rowspan="1" colspan="1">5:131.78 (T:0.373)</td><td align="center" valign="top" rowspan="1" colspan="1">DBP</td><td align="center" valign="top" rowspan="1" colspan="1">1.59 x 10<sup>-6</sup></td><td align="center" valign="top" rowspan="1" colspan="1">3.03 x 10<sup>-7</sup></td><td align="center" valign="top" rowspan="1" colspan="1">122,795</td><td align="center" valign="top" rowspan="1" colspan="1">-0.18</td><td align="center" valign="top" rowspan="1" colspan="1">2.29 x 10<sup>-5</sup></td><td align="center" valign="top" rowspan="1" colspan="1">282,023</td><td align="center" valign="top" rowspan="1" colspan="1">-0.19</td><td align="center" valign="top" rowspan="1" colspan="1">6.12 x 10<sup>-11</sup></td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"><italic>PHACTR1</italic></td><td align="center" valign="top" rowspan="1" colspan="1">rs9349379</td><td align="left" valign="top" rowspan="1" colspan="1">6:12.90 (A:0.566)</td><td align="center" valign="top" rowspan="1" colspan="1">SBP</td><td align="center" valign="top" rowspan="1" colspan="1">2.11 x 10<sup>-8</sup></td><td align="center" valign="top" rowspan="1" colspan="1">1.78 x 10<sup>-7</sup></td><td align="center" valign="top" rowspan="1" colspan="1">122,809</td><td align="center" valign="top" rowspan="1" colspan="1">0.24</td><td align="center" valign="top" rowspan="1" colspan="1">4.06 x 10<sup>-4</sup></td><td align="center" valign="top" rowspan="1" colspan="1">284,673</td><td align="center" valign="top" rowspan="1" colspan="1">0.29</td><td align="center" valign="top" rowspan="1" colspan="1">8.84 x 10<sup>-10</sup></td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"><italic>COL21A1</italic></td><td align="center" valign="top" rowspan="1" colspan="1">rs200999181<xref ref-type="table-fn" rid="TFN3">†</xref></td><td align="left" valign="top" rowspan="1" colspan="1">6:55.94 (A:0.002)</td><td align="center" valign="top" rowspan="1" colspan="1">PP</td><td align="center" valign="top" rowspan="1" colspan="1">3.08 x 10<sup>-8</sup></td><td align="center" valign="top" rowspan="1" colspan="1">2.46 x 10<sup>-7</sup></td><td align="center" valign="top" rowspan="1" colspan="1">121,487</td><td align="center" valign="top" rowspan="1" colspan="1">2.70</td><td align="center" valign="top" rowspan="1" colspan="1">1.90 x 10<sup>-4</sup></td><td align="center" valign="top" rowspan="1" colspan="1">242,486</td><td align="center" valign="top" rowspan="1" colspan="1">3.25</td><td align="center" valign="top" rowspan="1" colspan="1">6.27 x 10<sup>-10</sup></td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"><italic>ABO</italic></td><td align="center" valign="top" rowspan="1" colspan="1">rs687621</td><td align="left" valign="top" rowspan="1" colspan="1">9:136.14 (A:0.615)</td><td align="center" valign="top" rowspan="1" colspan="1">DBP</td><td align="center" valign="top" rowspan="1" colspan="1">8.80 x 10<sup>-8</sup></td><td align="center" valign="top" rowspan="1" colspan="1">2.55 x 10<sup>-7</sup></td><td align="center" valign="top" rowspan="1" colspan="1">122,798</td><td align="center" valign="top" rowspan="1" colspan="1">0.16</td><td align="center" valign="top" rowspan="1" colspan="1">1.96 x 10<sup>-4</sup></td><td align="center" valign="top" rowspan="1" colspan="1">276,014</td><td align="center" valign="top" rowspan="1" colspan="1">0.19</td><td align="center" valign="top" rowspan="1" colspan="1">5.45 x 10<sup>-10</sup></td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"><italic>ADO</italic></td><td align="center" valign="top" rowspan="1" colspan="1">rs10995311</td><td align="left" valign="top" rowspan="1" colspan="1">10:64.56 (C:0.567)</td><td align="center" valign="top" rowspan="1" colspan="1">DBP</td><td align="center" valign="top" rowspan="1" colspan="1">1.86 x 10<sup>-6</sup></td><td align="center" valign="top" rowspan="1" colspan="1">1.14 x 10<sup>-6</sup></td><td align="center" valign="top" rowspan="1" colspan="1">122,798</td><td align="center" valign="top" rowspan="1" colspan="1">0.23</td><td align="center" valign="top" rowspan="1" colspan="1">8.47 x 10<sup>-8</sup></td><td align="center" valign="top" rowspan="1" colspan="1">266,456</td><td align="center" valign="top" rowspan="1" colspan="1">0.21</td><td align="center" valign="top" rowspan="1" colspan="1">1.12 x 10<sup>-12</sup></td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"><italic>LMO1</italic></td><td align="center" valign="top" rowspan="1" colspan="1">rs110419</td><td align="left" valign="top" rowspan="1" colspan="1">11:8.25 (A:0.48)</td><td align="center" valign="top" rowspan="1" colspan="1">DBP</td><td align="center" valign="top" rowspan="1" colspan="1">9.41 x 10<sup>-6</sup></td><td align="center" valign="top" rowspan="1" colspan="1">2.22 x 10<sup>-5</sup></td><td align="center" valign="top" rowspan="1" colspan="1">122,798</td><td align="center" valign="top" rowspan="1" colspan="1">0.16</td><td align="center" valign="top" rowspan="1" colspan="1">1.81 x 10<sup>-4</sup></td><td align="center" valign="top" rowspan="1" colspan="1">279,935</td><td align="center" valign="top" rowspan="1" colspan="1">0.16</td><td align="center" valign="top" rowspan="1" colspan="1">3.04 x 10<sup>-8</sup></td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"><italic>OR5B12</italic></td><td align="center" valign="top" rowspan="1" colspan="1">rs11229457</td><td align="left" valign="top" rowspan="1" colspan="1">11:58.21 (T:0.236)</td><td align="center" valign="top" rowspan="1" colspan="1">SBP</td><td align="center" valign="top" rowspan="1" colspan="1">1.58 x 10<sup>-6</sup></td><td align="center" valign="top" rowspan="1" colspan="1">4.62 x 10<sup>-5</sup></td><td align="center" valign="top" rowspan="1" colspan="1">122,809</td><td align="center" valign="top" rowspan="1" colspan="1">-0.32</td><td align="center" valign="top" rowspan="1" colspan="1">7.53 x 10<sup>-5</sup></td><td align="center" valign="top" rowspan="1" colspan="1">284,680</td><td align="center" valign="top" rowspan="1" colspan="1">-0.31</td><td align="center" valign="top" rowspan="1" colspan="1">2.70 x 10<sup>-8</sup></td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"><italic>CERS5</italic></td><td align="center" valign="top" rowspan="1" colspan="1">rs7302981</td><td align="left" valign="top" rowspan="1" colspan="1">12:50.54 (A:0.361)</td><td align="center" valign="top" rowspan="1" colspan="1">DBP</td><td align="center" valign="top" rowspan="1" colspan="1">1.35 x 10<sup>-13</sup></td><td align="center" valign="top" rowspan="1" colspan="1">4.60 x 10<sup>-11</sup></td><td align="center" valign="top" rowspan="1" colspan="1">122,798</td><td align="center" valign="top" rowspan="1" colspan="1">0.24</td><td align="center" valign="top" rowspan="1" colspan="1">2.64 x 10<sup>-8</sup></td><td align="center" valign="top" rowspan="1" colspan="1">284,718</td><td align="center" valign="top" rowspan="1" colspan="1">0.25</td><td align="center" valign="top" rowspan="1" colspan="1">1.38 x 10<sup>-17</sup></td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"><italic>MYH6</italic></td><td align="center" valign="top" rowspan="1" colspan="1">rs452036</td><td align="left" valign="top" rowspan="1" colspan="1">14:23.87 (A:0.327)</td><td align="center" valign="top" rowspan="1" colspan="1">PP</td><td align="center" valign="top" rowspan="1" colspan="1">4.59 x 10<sup>-11</sup></td><td align="center" valign="top" rowspan="1" colspan="1">2.80 x 10<sup>-13</sup></td><td align="center" valign="top" rowspan="1" colspan="1">122,780</td><td align="center" valign="top" rowspan="1" colspan="1">-0.21</td><td align="center" valign="top" rowspan="1" colspan="1">1.81 x 10<sup>-5</sup></td><td align="center" valign="top" rowspan="1" colspan="1">284,672</td><td align="center" valign="top" rowspan="1" colspan="1">-0.28</td><td align="center" valign="top" rowspan="1" colspan="1">2.96 x 10<sup>-16</sup></td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"><italic>DPEP1</italic></td><td align="center" valign="top" rowspan="1" colspan="1">rs1126464</td><td align="left" valign="top" rowspan="1" colspan="1">16:89.70 (C:0.256)</td><td align="center" valign="top" rowspan="1" colspan="1">DBP</td><td align="center" valign="top" rowspan="1" colspan="1">1.19 x 10<sup>-9</sup></td><td align="center" valign="top" rowspan="1" colspan="1">4.35 x 10<sup>-11</sup></td><td align="center" valign="top" rowspan="1" colspan="1">118,677</td><td align="center" valign="top" rowspan="1" colspan="1">0.24</td><td align="center" valign="top" rowspan="1" colspan="1">1.68 x 10<sup>-6</sup></td><td align="center" valign="top" rowspan="1" colspan="1">261,564</td><td align="center" valign="top" rowspan="1" colspan="1">0.28</td><td align="center" valign="top" rowspan="1" colspan="1">1.02 x 10<sup>-15</sup></td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"><italic>TBX2</italic></td><td align="center" valign="top" rowspan="1" colspan="1">rs8068318<xref ref-type="table-fn" rid="TFN3">†</xref></td><td align="left" valign="top" rowspan="1" colspan="1">17:59.48 (T:0.698)</td><td align="center" valign="top" rowspan="1" colspan="1">DBP</td><td align="center" valign="top" rowspan="1" colspan="1">7.46 x 10<sup>-13</sup></td><td align="center" valign="top" rowspan="1" colspan="1">5.71 x 10<sup>-10</sup></td><td align="center" valign="top" rowspan="1" colspan="1">122,798</td><td align="center" valign="top" rowspan="1" colspan="1">0.26</td><td align="center" valign="top" rowspan="1" colspan="1">3.23 x 10<sup>-8</sup></td><td align="center" valign="top" rowspan="1" colspan="1">281,978</td><td align="center" valign="top" rowspan="1" colspan="1">0.26</td><td align="center" valign="top" rowspan="1" colspan="1">1.95 x 10<sup>-16</sup></td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"><italic>RGL3</italic></td><td align="center" valign="top" rowspan="1" colspan="1">rs167479</td><td align="left" valign="top" rowspan="1" colspan="1">19:11.53 (T:0.486)</td><td align="center" valign="top" rowspan="1" colspan="1">DBP</td><td align="center" valign="top" rowspan="1" colspan="1">2.22 x 10<sup>-23</sup></td><td align="center" valign="top" rowspan="1" colspan="1">1.97 x 10<sup>-22</sup></td><td align="center" valign="top" rowspan="1" colspan="1">122,797</td><td align="center" valign="top" rowspan="1" colspan="1">-0.29</td><td align="center" valign="top" rowspan="1" colspan="1">3.01 x 10<sup>-11</sup></td><td align="center" valign="top" rowspan="1" colspan="1">283,332</td><td align="center" valign="top" rowspan="1" colspan="1">-0.33</td><td align="center" valign="top" rowspan="1" colspan="1">1.99 x 10<sup>-31</sup></td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"><italic>PREX1</italic></td><td align="center" valign="top" rowspan="1" colspan="1">rs6095241</td><td align="left" valign="top" rowspan="1" colspan="1">20:47.31 (A:0.452)</td><td align="center" valign="top" rowspan="1" colspan="1">DBP</td><td align="center" valign="top" rowspan="1" colspan="1">5.65 x 10<sup>-6</sup></td><td align="center" valign="top" rowspan="1" colspan="1">2.29 x 10<sup>-5</sup></td><td align="center" valign="top" rowspan="1" colspan="1">122,798</td><td align="center" valign="top" rowspan="1" colspan="1">-0.18</td><td align="center" valign="top" rowspan="1" colspan="1">2.56 x 10<sup>-5</sup></td><td align="center" valign="top" rowspan="1" colspan="1">281,322</td><td align="center" valign="top" rowspan="1" colspan="1">-0.17</td><td align="center" valign="top" rowspan="1" colspan="1">4.75 x 10<sup>-9</sup></td></tr><tr><td align="left" valign="top" colspan="12" rowspan="1"><bold>ALL ancestry</bold></td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"><italic>RBM47</italic></td><td align="center" valign="top" rowspan="1" colspan="1">rs35529250<xref ref-type="table-fn" rid="TFN3">†</xref></td><td align="left" valign="top" rowspan="1" colspan="1">4:40.43 (T:0.01)</td><td align="center" valign="top" rowspan="1" colspan="1">SBP</td><td align="center" valign="top" rowspan="1" colspan="1">6.56 x 10<sup>-7</sup></td><td align="center" valign="top" rowspan="1" colspan="1">6.15 x 10<sup>-6</sup></td><td align="center" valign="top" rowspan="1" colspan="1">148,878</td><td align="center" valign="top" rowspan="1" colspan="1">-1.43</td><td align="center" valign="top" rowspan="1" colspan="1">5.02 x 10<sup>-4</sup></td><td align="center" valign="top" rowspan="1" colspan="1">306,352</td><td align="center" valign="top" rowspan="1" colspan="1">-1.55</td><td align="center" valign="top" rowspan="1" colspan="1">2.42 x 10<sup>-8</sup></td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"><italic>OBFC1</italic></td><td align="center" valign="top" rowspan="1" colspan="1">rs4387287</td><td align="left" valign="top" rowspan="1" colspan="1">10:105.68 (A:0.157)</td><td align="center" valign="top" rowspan="1" colspan="1">SBP</td><td align="center" valign="top" rowspan="1" colspan="1">2.23 x 10<sup>-8</sup></td><td align="center" valign="top" rowspan="1" colspan="1">1.32 x 10<sup>-7</sup></td><td align="center" valign="top" rowspan="1" colspan="1">147,791</td><td align="center" valign="top" rowspan="1" colspan="1">0.28</td><td align="center" valign="top" rowspan="1" colspan="1">3.37 x 10<sup>-4</sup></td><td align="center" valign="top" rowspan="1" colspan="1">320,494</td><td align="center" valign="top" rowspan="1" colspan="1">0.36</td><td align="center" valign="top" rowspan="1" colspan="1">9.12 x 10<sup>-10</sup></td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"><italic>RRAS</italic></td><td align="center" valign="top" rowspan="1" colspan="1">rs61760904<xref ref-type="table-fn" rid="TFN3">†</xref></td><td align="left" valign="top" rowspan="1" colspan="1">19:50.14 (T:0.008)</td><td align="center" valign="top" rowspan="1" colspan="1">SBP</td><td align="center" valign="top" rowspan="1" colspan="1">1.96 x 10<sup>-6</sup></td><td align="center" valign="top" rowspan="1" colspan="1">1.90 x 10<sup>-5</sup></td><td align="center" valign="top" rowspan="1" colspan="1">148,878</td><td align="center" valign="top" rowspan="1" colspan="1">1.38</td><td align="center" valign="top" rowspan="1" colspan="1">5.70 x 10<sup>-4</sup></td><td align="center" valign="top" rowspan="1" colspan="1">322,664</td><td align="center" valign="top" rowspan="1" colspan="1">1.50</td><td align="center" valign="top" rowspan="1" colspan="1">8.45 x 10<sup>-8</sup></td></tr></tbody></table><table-wrap-foot><fn id="TFN1"><p id="P77">SNV-BP associations are reported for the newly identified BP loci that replicated at <italic>P</italic> < 6.2 x 10<sup>-4</sup> (Bonferroni correction for the 81 variants selected for replication for a primary blood pressure trait; <xref ref-type="sec" rid="S11">Methods</xref>). Loci are categorised into EUR and ALL ancestry based on the meta-analysis used to replicate the variants for the primary BP trait shown in columns labelled ‘Trait’. In the columns that contains the discovery meta-analyses results, <italic>P</italic><sub>t</sub> represents the <italic>P</italic>-value for association of the variant with the transformed primary BP trait in the EUR_SAS discovery meta-analyses (which was also used to select the variant for replication) and <italic>P</italic><sub>u</sub> represents the <italic>P</italic>-value for association with the untransformed primary BP trait in the ancestry in which the variant replicated. N, <bold>β</bold> and <italic>P</italic>, which denote the number of samples, estimated allelic effect and <italic>P</italic>-value for association with the primary BP trait, are provided for the untransformed primary BP trait in the replication data and also from the combined (discovery and replication) meta-analyses. NB: ALL ancestry corresponds to all ancestries in the combined (discovery + replication) meta-analyses</p></fn><fn id="TFN2"><p id="P78">Locus – Gene or region containing the SNV, rsID - dbSNP rsID. Chr:Pos (EA:EAF) – Chromosome:NCBI Build 37 position in Mb (effect allele:effect allele frequency), Trait – primary blood pressure trait for which the variant was and also replicated, β - effect estimate, N:sample size, EUR - European.</p></fn><fn id="TFN3"><label>†</label><p id="P79">indicates it is a non-synonymous SNV (nsSNV) or is in linkage disequilibrium with a nsSNV (r<sup>2</sup> > 0.8) that is predicted to be damaging</p></fn></table-wrap-foot></table-wrap><table-wrap id="T2" position="float" orientation="portrait"><label>Table 2</label><caption><title>Novel blood pressure trait associated loci. Variants with GWS evidence of association in combined meta-analyses</title></caption><table frame="hsides" rules="groups"><thead><tr><th align="center" colspan="3" valign="top" rowspan="1">Variant information</th><th align="center" rowspan="1" colspan="1"></th><th align="center" colspan="2" valign="top" rowspan="1">Discovery<hr></hr></th><th align="center" colspan="3" valign="top" rowspan="1">Replication</th><th align="center" colspan="3" valign="top" rowspan="1">Combined<hr></hr></th></tr><tr><th align="center" rowspan="1" colspan="1">Locus</th><th align="center" rowspan="1" colspan="1">rsID</th><th align="center" rowspan="1" colspan="1">Chr:Pos (EA:EAF)</th><th align="center" rowspan="1" colspan="1">Trait</th><th align="center" rowspan="1" colspan="1"><italic>P<sub>t</sub></italic></th><th align="center" rowspan="1" colspan="1"><italic>P<sub>U</sub></italic></th><th align="center" rowspan="1" colspan="1">N</th><th align="center" rowspan="1" colspan="1">β</th><th align="center" rowspan="1" colspan="1"><italic>P</italic></th><th align="center" rowspan="1" colspan="1">N</th><th align="center" rowspan="1" colspan="1">β</th><th align="center" rowspan="1" colspan="1"><italic>P</italic></th></tr></thead><tbody><tr><td align="left" colspan="12" rowspan="1"><bold>EUR</bold></td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">2q36.3</td><td align="center" valign="top" rowspan="1" colspan="1">rs2972146</td><td align="center" valign="top" rowspan="1" colspan="1">2:227.10 (T:0.652)</td><td align="center" valign="top" rowspan="1" colspan="1">DBP<xref ref-type="table-fn" rid="TFN6">§</xref><break></break>(HTN)</td><td align="center" valign="top" rowspan="1" colspan="1">1.51 x 10<sup>-9</sup></td><td align="center" valign="top" rowspan="1" colspan="1">2.47 x 10<sup>-7</sup></td><td align="center" valign="top" rowspan="1" colspan="1">122,798</td><td align="center" valign="top" rowspan="1" colspan="1">0.13</td><td align="center" valign="top" rowspan="1" colspan="1">2.20 x 10<sup>-3</sup></td><td align="center" valign="top" rowspan="1" colspan="1">275,610</td><td align="center" rowspan="1" colspan="1">0.17</td><td align="center" valign="top" rowspan="1" colspan="1">8.40 x 10<sup>-9</sup></td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"><italic>ZBTB38</italic></td><td align="center" valign="top" rowspan="1" colspan="1">rs16851397</td><td align="center" valign="top" rowspan="1" colspan="1">3:141.13 (A:0.953)</td><td align="center" valign="top" rowspan="1" colspan="1">DBP<xref ref-type="table-fn" rid="TFN6">§</xref><break></break>(SBP)</td><td align="center" valign="top" rowspan="1" colspan="1">6.87 x 10<sup>-6</sup></td><td align="center" valign="top" rowspan="1" colspan="1">3.20 x 10<sup>-5</sup></td><td align="center" valign="top" rowspan="1" colspan="1">122,798</td><td align="center" valign="top" rowspan="1" colspan="1">-0.38</td><td align="center" valign="top" rowspan="1" colspan="1">1.20 x 10<sup>-4</sup></td><td align="center" valign="top" rowspan="1" colspan="1">284,717</td><td align="center" valign="top" rowspan="1" colspan="1">-0.38</td><td align="center" valign="top" rowspan="1" colspan="1">3.01 x 10<sup>-8</sup></td></tr><tr><td align="center" rowspan="1" colspan="1"><italic>PRDM6</italic></td><td align="center" rowspan="1" colspan="1">rs1008058</td><td align="center" rowspan="1" colspan="1">5:122.44 (A:0.135)</td><td align="center" rowspan="1" colspan="1">SBP</td><td align="center" rowspan="1" colspan="1">5.09 x 10<sup>-7</sup></td><td align="center" rowspan="1" colspan="1">1.01 x 10<sup>-8</sup></td><td align="center" rowspan="1" colspan="1">43,109</td><td align="center" rowspan="1" colspan="1">0.46</td><td align="center" rowspan="1" colspan="1">3.61 x 10<sup>-3</sup></td><td align="center" rowspan="1" colspan="1">176,362</td><td align="center" rowspan="1" colspan="1">0.55</td><td align="center" rowspan="1" colspan="1">2.99 x 10<sup>-10</sup></td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"><italic>GPR20</italic></td><td align="center" valign="top" rowspan="1" colspan="1">rs34591516</td><td align="center" valign="top" rowspan="1" colspan="1">8:142.37 (T:0.055)</td><td align="center" valign="top" rowspan="1" colspan="1">SBP<xref ref-type="table-fn" rid="TFN6">§</xref><break></break>(DBP)</td><td align="center" valign="top" rowspan="1" colspan="1">1.54 x 10<sup>-6</sup></td><td align="center" valign="top" rowspan="1" colspan="1">1.01 x 10<sup>-7</sup></td><td align="center" valign="top" rowspan="1" colspan="1">122,807</td><td align="center" valign="top" rowspan="1" colspan="1">0.51</td><td align="center" valign="top" rowspan="1" colspan="1">4.20 x 10<sup>-4</sup></td><td align="center" valign="top" rowspan="1" colspan="1">282,009</td><td align="center" valign="top" rowspan="1" colspan="1">0.64</td><td align="center" valign="top" rowspan="1" colspan="1">6.10 x 10<sup>-10</sup></td></tr><tr><td align="center" rowspan="1" colspan="1"><italic>HOXB7</italic></td><td align="center" rowspan="1" colspan="1">rs7406910</td><td align="center" rowspan="1" colspan="1">17:46.69 (T:0.118)</td><td align="center" rowspan="1" colspan="1">SBP</td><td align="center" rowspan="1" colspan="1">6.07 x 10<sup>-10</sup></td><td align="center" rowspan="1" colspan="1">2.74 x 10<sup>-9</sup></td><td align="center" rowspan="1" colspan="1">122,809</td><td align="center" rowspan="1" colspan="1">-0.20</td><td align="center" rowspan="1" colspan="1">4.89 x 10<sup>-2</sup></td><td align="center" rowspan="1" colspan="1">284,690</td><td align="center" rowspan="1" colspan="1">-0.46</td><td align="center" rowspan="1" colspan="1">3.80 x 10<sup>-8</sup></td></tr><tr><td align="center" rowspan="1" colspan="1"><italic>AMH</italic></td><td align="center" rowspan="1" colspan="1">rs10407022<xref ref-type="table-fn" rid="TFN7">†</xref></td><td align="center" rowspan="1" colspan="1">19:2.25 (T:0.82)</td><td align="center" rowspan="1" colspan="1">PP</td><td align="center" rowspan="1" colspan="1">1.63 x 10<sup>-7</sup></td><td align="center" rowspan="1" colspan="1">1.73 x 10<sup>-7</sup></td><td align="center" rowspan="1" colspan="1">118,656</td><td align="center" rowspan="1" colspan="1">-0.19</td><td align="center" rowspan="1" colspan="1">1.62 x 10<sup>-3</sup></td><td align="center" rowspan="1" colspan="1">252,525</td><td align="center" rowspan="1" colspan="1">-0.26</td><td align="center" rowspan="1" colspan="1">5.94 x 10<sup>-9</sup></td></tr><tr><td align="center" rowspan="1" colspan="1"><italic>ZNF101</italic></td><td align="center" rowspan="1" colspan="1">rs2304130</td><td align="center" rowspan="1" colspan="1">19:19.79 (A:0.914)</td><td align="center" rowspan="1" colspan="1">DBP</td><td align="center" rowspan="1" colspan="1">1.66 x 10<sup>-8</sup></td><td align="center" rowspan="1" colspan="1">1.92 x 10<sup>-8</sup></td><td align="center" rowspan="1" colspan="1">122,798</td><td align="center" rowspan="1" colspan="1">-0.17</td><td align="center" rowspan="1" colspan="1">1.71 x 10<sup>-2</sup></td><td align="center" rowspan="1" colspan="1">284,705</td><td align="center" rowspan="1" colspan="1">-0.29</td><td align="center" rowspan="1" colspan="1">1.53 x 10<sup>-8</sup></td></tr><tr><td align="center" rowspan="1" colspan="1"><italic>PROCR</italic></td><td align="center" rowspan="1" colspan="1">rs867186</td><td align="center" rowspan="1" colspan="1">20:33.76 (A:0.873)</td><td align="center" rowspan="1" colspan="1">DBP</td><td align="center" rowspan="1" colspan="1">1.44 x 10<sup>-6</sup></td><td align="center" rowspan="1" colspan="1">4.15 x 10<sup>-7</sup></td><td align="center" rowspan="1" colspan="1">122,798</td><td align="center" rowspan="1" colspan="1">0.21</td><td align="center" rowspan="1" colspan="1">2.48 x 10<sup>-3</sup></td><td align="center" rowspan="1" colspan="1">284,722</td><td align="center" rowspan="1" colspan="1">0.26</td><td align="center" rowspan="1" colspan="1">1.19 x 10<sup>-8</sup></td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"><italic>RRP1B</italic></td><td align="center" valign="top" rowspan="1" colspan="1">rs9306160</td><td align="center" valign="top" rowspan="1" colspan="1">21:45.11 (T:0.374)</td><td align="center" valign="top" rowspan="1" colspan="1">DBP<xref ref-type="table-fn" rid="TFN6">§</xref><break></break>(SBP)</td><td align="center" valign="top" rowspan="1" colspan="1">1.04 x 10<sup>-8</sup></td><td align="center" valign="top" rowspan="1" colspan="1">1.90 x 10<sup>-6</sup></td><td align="center" valign="top" rowspan="1" colspan="1">100,489</td><td align="center" valign="top" rowspan="1" colspan="1">-0.16</td><td align="center" valign="top" rowspan="1" colspan="1">4.30 x 10<sup>-4</sup></td><td align="center" valign="top" rowspan="1" colspan="1">249,817</td><td align="center" valign="top" rowspan="1" colspan="1">-0.18</td><td align="center" valign="top" rowspan="1" colspan="1">6.80 x 10<sup>-9</sup></td></tr><tr><td align="center" rowspan="1" colspan="1"><italic>TNRC6B</italic></td><td align="center" rowspan="1" colspan="1">rs470113</td><td align="center" rowspan="1" colspan="1">22:40.73 (A:0.804)</td><td align="center" rowspan="1" colspan="1">PP</td><td align="center" rowspan="1" colspan="1">1.48 x 10<sup>-10</sup></td><td align="center" rowspan="1" colspan="1">1.31 x 10<sup>-9</sup></td><td align="center" rowspan="1" colspan="1">122,780</td><td align="center" rowspan="1" colspan="1">-0.14</td><td align="center" rowspan="1" colspan="1">1.37 x 10<sup>-2</sup></td><td align="center" rowspan="1" colspan="1">284,683</td><td align="center" rowspan="1" colspan="1">-0.25</td><td align="center" rowspan="1" colspan="1">1.67 x 10<sup>-9</sup></td></tr><tr><td align="left" colspan="12" rowspan="1"><bold>ALL ancestry</bold></td></tr><tr><td align="center" rowspan="1" colspan="1">7q32.1</td><td align="center" rowspan="1" colspan="1">rs4728142</td><td align="center" rowspan="1" colspan="1">7:128.57 (A:0.433)</td><td align="center" rowspan="1" colspan="1">SBP</td><td align="center" rowspan="1" colspan="1">8.10 x 10<sup>-6</sup></td><td align="center" rowspan="1" colspan="1">4.21 x 10<sup>-6</sup></td><td align="center" rowspan="1" colspan="1">150,542</td><td align="center" rowspan="1" colspan="1">-0.21</td><td align="center" rowspan="1" colspan="1">8.62 x 10<sup>-4</sup></td><td align="center" rowspan="1" colspan="1">338,338</td><td align="center" rowspan="1" colspan="1">-0.24</td><td align="center" rowspan="1" colspan="1">3.45 x 10<sup>-8</sup></td></tr><tr><td align="center" rowspan="1" colspan="1"><italic>PRKAG1</italic></td><td align="center" rowspan="1" colspan="1">rs1126930<xref ref-type="table-fn" rid="TFN7">†</xref></td><td align="center" rowspan="1" colspan="1">12:49.40 (C:0.036)</td><td align="center" rowspan="1" colspan="1">PP</td><td align="center" rowspan="1" colspan="1">2.12 x 10<sup>-6</sup></td><td align="center" rowspan="1" colspan="1">4.62 x 10<sup>-7</sup></td><td align="center" rowspan="1" colspan="1">151,481</td><td align="center" rowspan="1" colspan="1">0.36</td><td align="center" rowspan="1" colspan="1">3.74 x 10<sup>-3</sup></td><td align="center" rowspan="1" colspan="1">314,894</td><td align="center" rowspan="1" colspan="1">0.50</td><td align="center" rowspan="1" colspan="1">3.34 x 10<sup>-8</sup></td></tr><tr><td align="center" rowspan="1" colspan="1"><italic>SBNO1</italic></td><td align="center" rowspan="1" colspan="1">rs1060105</td><td align="center" rowspan="1" colspan="1">12:123.81 (T:0.209)</td><td align="center" rowspan="1" colspan="1">DBP</td><td align="center" rowspan="1" colspan="1">6.66 x 10<sup>-7</sup></td><td align="center" rowspan="1" colspan="1">1.09 x 10<sup>-6</sup></td><td align="center" rowspan="1" colspan="1">150,532</td><td align="center" rowspan="1" colspan="1">-0.15</td><td align="center" rowspan="1" colspan="1">2.67 x 10<sup>-3</sup></td><td align="center" rowspan="1" colspan="1">336,413</td><td align="center" rowspan="1" colspan="1">-0.18</td><td align="center" rowspan="1" colspan="1">3.07 x 10<sup>-8</sup></td></tr></tbody></table><table-wrap-foot><fn id="TFN4"><p id="P80">SNV-BP associations are reported for the newly identified BP loci that showed genome-wide significant association (<italic>P</italic> < 5 x 10<sup>-8</sup>) in the combined discovery and replication meta-analyses. In the columns that contain results from the discovery meta-analyses, <italic>P</italic><sub>t</sub> represents the <italic>P</italic>-value for association of the variant with the transformed <italic>primary</italic> BP trait in the EUR_SAS discovery meta-analyses (used to select the variant for replication) and <italic>P</italic><sub>u</sub> represents the <italic>P</italic>-value for association with the untransformed BP trait in the ancestry in which the variant was validated. Loci are categorised into EUR and ALL ancestry based on the ancestry in which the variant showed association with a blood pressure trait at <italic>P</italic> < 5 x 10<sup>-8</sup>. N, <bold>β</bold> and <italic>P</italic>, which denote the number of samples, estimated allelic effect and <italic>P</italic>-value for association with the validated BP trait, are provided for the untransformed BP trait in the replication data and also from the combined (discovery and replication) meta-analyses. NB: ALL ancestry corresponds to all ancestries in the combined (discovery + replication) meta-analyses.</p></fn><fn id="TFN5"><p id="P81">Locus – Gene or region containing the SNV, rsID - dbSNP rsID. Chr:Pos (EA:EAF) – Chromosome:NCBI Build 37 position in Mb (effect allele:effect allele frequency), Trait - blood pressure trait for which association is reported, EUR - European.</p></fn><fn id="TFN6"><label>§</label><p id="P82">At four loci (2q36.3, <italic>ZBTB38, GPR20</italic> and <italic>RRP1B</italic>) the primary trait used to select the variants for replication is given in parentheses because the variant associations were validated in the combined meta-analysis for the listed secondary trait. For these variants, <italic>P</italic><sub>t</sub> denotes the <italic>P</italic>-value for association with the primary trait, the other <italic>P</italic>-values provided are for the secondary trait.</p></fn><fn id="TFN7"><label>†</label><p id="P83">indicates it is a non-synonymous SNV (nsSNV) or is linkage disequilibrium with a nsSNV (r<sup>2</sup> > 0.8) that is predicted to be damaging</p></fn></table-wrap-foot></table-wrap><table-wrap id="T3" position="float" orientation="landscape"><label>Table 3</label><caption><title>Results of the genetic risk score analyses across CVD traits and risk factors.</title></caption><table frame="hsides" rules="groups"><thead><tr><th align="center" valign="top" rowspan="1" colspan="1">Outcome</th><th align="center" valign="top" rowspan="1" colspan="1">Units</th><th align="center" valign="top" rowspan="1" colspan="1">N</th><th align="center" colspan="2" valign="top" rowspan="1">DBP (per 10mmHg increase)</th><th align="center" colspan="2" valign="top" rowspan="1">SBP (per 10mmHg increase)</th><th align="center" colspan="2" valign="top" rowspan="1">PP (per 10mmHg increase)</th></tr><tr><th align="left" rowspan="1" colspan="1"></th><th align="left" rowspan="1" colspan="1"></th><th align="left" rowspan="1" colspan="1"></th><th colspan="6" align="left" valign="top" rowspan="1"><hr></hr></th></tr><tr><th align="left" rowspan="1" colspan="1"></th><th align="left" rowspan="1" colspan="1"></th><th align="left" rowspan="1" colspan="1"></th><th align="center" rowspan="1" colspan="1">Effect [95% CI]</th><th align="center" rowspan="1" colspan="1"><italic>P</italic></th><th align="center" rowspan="1" colspan="1">Effect [95% CI]</th><th align="center" rowspan="1" colspan="1"><italic>P</italic></th><th align="center" rowspan="1" colspan="1">Effect [95% CI]</th><th align="center" rowspan="1" colspan="1"><italic>P</italic></th></tr></thead><tbody><tr><td align="left" rowspan="1" colspan="1">CHD</td><td align="center" rowspan="1" colspan="1">OR</td><td align="center" rowspan="1" colspan="1">82,056</td><td align="center" rowspan="1" colspan="1">1.62 [ 1.28, 2.05]</td><td align="center" rowspan="1" colspan="1">5.99 x 10<sup>-5</sup></td><td align="center" rowspan="1" colspan="1">1.39 [ 1.22, 1.59]</td><td align="center" rowspan="1" colspan="1">6.07 x 10<sup>-7</sup></td><td align="center" rowspan="1" colspan="1">1.70 [ 1.34, 2.16]</td><td align="center" rowspan="1" colspan="1">1.20 x 10<sup>-5</sup></td></tr><tr><td align="left" rowspan="1" colspan="1">Ischemic stroke</td><td align="center" rowspan="1" colspan="1">OR</td><td align="center" rowspan="1" colspan="1">25,799</td><td align="center" rowspan="1" colspan="1">1.93 [ 1.47, 2.55]</td><td align="center" rowspan="1" colspan="1">2.81 x 10<sup>-6</sup></td><td align="center" rowspan="1" colspan="1">1.57 [ 1.35, 1.84]</td><td align="center" rowspan="1" colspan="1">1.16 x 10<sup>-8</sup></td><td align="center" rowspan="1" colspan="1">2.12 [ 1.58, 2.84]</td><td align="center" rowspan="1" colspan="1">5.35 x 10<sup>-7</sup></td></tr><tr><td align="left" rowspan="1" colspan="1">Cardioembolic stroke</td><td align="center" rowspan="1" colspan="1">OR</td><td align="center" rowspan="1" colspan="1">16,113</td><td align="center" rowspan="1" colspan="1">1.43 [ 0.86, 2.39]</td><td align="center" rowspan="1" colspan="1">0.1683</td><td align="center" rowspan="1" colspan="1">1.33 [ 0.99, 1.80]</td><td align="center" rowspan="1" colspan="1">0.0584</td><td align="center" rowspan="1" colspan="1">1.73 [ 1.00, 3.02]</td><td align="center" rowspan="1" colspan="1">0.0518</td></tr><tr><td align="left" rowspan="1" colspan="1">Large vessel stroke</td><td align="center" rowspan="1" colspan="1">OR</td><td align="center" rowspan="1" colspan="1">13,903</td><td align="center" rowspan="1" colspan="1">2.26 [ 1.25, 4.08]</td><td align="center" rowspan="1" colspan="1">0.0068</td><td align="center" rowspan="1" colspan="1">1.85 [ 1.32, 2.59]</td><td align="center" rowspan="1" colspan="1">3.61 x 10<sup>-4</sup></td><td align="center" rowspan="1" colspan="1">3.05 [ 1.64, 5.68]</td><td align="center" rowspan="1" colspan="1">4.37 x 10<sup>-4</sup></td></tr><tr><td align="left" rowspan="1" colspan="1">Small vessel stroke</td><td align="center" rowspan="1" colspan="1">OR</td><td align="center" rowspan="1" colspan="1">15,617</td><td align="center" rowspan="1" colspan="1">1.96 [ 1.13, 3.41]</td><td align="center" rowspan="1" colspan="1">0.0168</td><td align="center" rowspan="1" colspan="1">1.56 [ 1.13, 2.16]</td><td align="center" rowspan="1" colspan="1">0.0064</td><td align="center" rowspan="1" colspan="1">1.98 [ 1.09, 3.61]</td><td align="center" rowspan="1" colspan="1">0.0248</td></tr><tr><td align="left" rowspan="1" colspan="1">Heart failure</td><td align="center" rowspan="1" colspan="1">OR</td><td align="center" rowspan="1" colspan="1">13,282</td><td align="center" rowspan="1" colspan="1">1.48 [ 1.02, 2.17]</td><td align="center" rowspan="1" colspan="1">0.0409</td><td align="center" rowspan="1" colspan="1">1.25 [ 1.00, 1.57]</td><td align="center" rowspan="1" colspan="1">0.0512</td><td align="center" rowspan="1" colspan="1">1.33 [ 0.88, 2.02]</td><td align="center" rowspan="1" colspan="1">0.1757</td></tr><tr><td align="left" rowspan="1" colspan="1">Left ventricular mass</td><td align="center" rowspan="1" colspan="1">g</td><td align="center" rowspan="1" colspan="1">11,273</td><td align="center" rowspan="1" colspan="1">9.57 [ 3.98,15.17]</td><td align="center" rowspan="1" colspan="1">8.02 x 10<sup>-4</sup></td><td align="center" rowspan="1" colspan="1">5.13 [ 1.77, 8.48]</td><td align="center" rowspan="1" colspan="1">0.0027</td><td align="center" rowspan="1" colspan="1">5.97 [-0.38,12.31]</td><td align="center" rowspan="1" colspan="1">0.0653</td></tr><tr><td align="left" rowspan="1" colspan="1">Left ventricular wall thickness</td><td align="center" rowspan="1" colspan="1">cm</td><td align="center" rowspan="1" colspan="1">11,311</td><td align="center" rowspan="1" colspan="1">0.10 [ 0.06, 0.13]</td><td align="center" rowspan="1" colspan="1">1.88 x 10<sup>-8</sup></td><td align="center" rowspan="1" colspan="1">0.05 [ 0.03, 0.07]</td><td align="center" rowspan="1" colspan="1">5.52 x 10<sup>-6</sup></td><td align="center" rowspan="1" colspan="1">0.05 [ 0.01, 0.09]</td><td align="center" rowspan="1" colspan="1">0.0187</td></tr><tr><td align="left" rowspan="1" colspan="1">HDL</td><td align="center" rowspan="1" colspan="1">mg/dl</td><td align="center" rowspan="1" colspan="1">80,395</td><td align="center" rowspan="1" colspan="1">0.25 [-1.00, 1.51]</td><td align="center" rowspan="1" colspan="1">0.6930</td><td align="center" rowspan="1" colspan="1">0.21 [-0.50, 0.92]</td><td align="center" rowspan="1" colspan="1">0.5622</td><td align="center" rowspan="1" colspan="1">0.47 [-0.79, 1.73]</td><td align="center" rowspan="1" colspan="1">0.4668</td></tr><tr><td align="left" rowspan="1" colspan="1">LDL</td><td align="center" rowspan="1" colspan="1">mg/dl</td><td align="center" rowspan="1" colspan="1">77,021</td><td align="center" rowspan="1" colspan="1">-1.57 [-5.20, 2.06]</td><td align="center" rowspan="1" colspan="1">0.3972</td><td align="center" rowspan="1" colspan="1">0.07 [-2.03, 2.16]</td><td align="center" rowspan="1" colspan="1">0.9498</td><td align="center" rowspan="1" colspan="1">1.87 [-1.86, 5.59]</td><td align="center" rowspan="1" colspan="1">0.3255</td></tr><tr><td align="left" rowspan="1" colspan="1">Total cholesterol</td><td align="center" rowspan="1" colspan="1">mg/dl</td><td align="center" rowspan="1" colspan="1">80,455</td><td align="center" rowspan="1" colspan="1">-1.34 [-5.90, 3.22]</td><td align="center" rowspan="1" colspan="1">0.5639</td><td align="center" rowspan="1" colspan="1">0.70 [-1.93, 3.32]</td><td align="center" rowspan="1" colspan="1">0.6029</td><td align="center" rowspan="1" colspan="1">3.68 [-0.97, 8.33]</td><td align="center" rowspan="1" colspan="1">0.1209</td></tr><tr><td align="left" rowspan="1" colspan="1">Triglycerides</td><td align="center" rowspan="1" colspan="1">mg/dl</td><td align="center" rowspan="1" colspan="1">77,779</td><td align="center" rowspan="1" colspan="1">0.02 [-0.03, 0.08]</td><td align="center" rowspan="1" colspan="1">0.3859</td><td align="center" rowspan="1" colspan="1">0.02 [-0.01, 0.05]</td><td align="center" rowspan="1" colspan="1">0.2697</td><td align="center" rowspan="1" colspan="1">0.03 [-0.03, 0.08]</td><td align="center" rowspan="1" colspan="1">0.3025</td></tr><tr><td align="left" rowspan="1" colspan="1">BMI</td><td align="center" rowspan="1" colspan="1">INVT</td><td align="center" rowspan="1" colspan="1">526,508</td><td align="center" rowspan="1" colspan="1">-0.10 [-0.18,-0.01]</td><td align="center" rowspan="1" colspan="1">0.0342</td><td align="center" rowspan="1" colspan="1">-0.07 [-0.13,-0.02]</td><td align="center" rowspan="1" colspan="1">0.0058</td><td align="center" rowspan="1" colspan="1">-0.12 [-0.23,-0.02]</td><td align="center" rowspan="1" colspan="1">0.0165</td></tr><tr><td align="left" rowspan="1" colspan="1">WHRadjBMI</td><td align="center" rowspan="1" colspan="1">INVT</td><td align="center" rowspan="1" colspan="1">344,369</td><td align="center" rowspan="1" colspan="1">0.03 [-0.04, 0.11]</td><td align="center" rowspan="1" colspan="1">0.4025</td><td align="center" rowspan="1" colspan="1">0.03 [-0.02, 0.08]</td><td align="center" rowspan="1" colspan="1">0.2170</td><td align="center" rowspan="1" colspan="1">0.06 [-0.03, 0.15]</td><td align="center" rowspan="1" colspan="1">0.1885</td></tr><tr><td align="left" rowspan="1" colspan="1">Height</td><td align="center" rowspan="1" colspan="1">INVT</td><td align="center" rowspan="1" colspan="1">458,927</td><td align="center" rowspan="1" colspan="1">0.02 [-0.15, 0.18]</td><td align="center" rowspan="1" colspan="1">0.8592</td><td align="center" rowspan="1" colspan="1">-0.04 [-0.15, 0.06]</td><td align="center" rowspan="1" colspan="1">0.4170</td><td align="center" rowspan="1" colspan="1">-0.18 [-0.37, 0.01]</td><td align="center" rowspan="1" colspan="1">0.0683</td></tr><tr><td align="left" rowspan="1" colspan="1">eGFR</td><td align="center" rowspan="1" colspan="1">INVT</td><td align="center" rowspan="1" colspan="1">51,039</td><td align="center" rowspan="1" colspan="1">-0.02 [-0.15, 0.11]</td><td align="center" rowspan="1" colspan="1">0.7810</td><td align="center" rowspan="1" colspan="1">-0.03 [-0.10, 0.04]</td><td align="center" rowspan="1" colspan="1">0.4080</td><td align="center" rowspan="1" colspan="1">-0.07 [-0.20, 0.06]</td><td align="center" rowspan="1" colspan="1">0.2741</td></tr></tbody></table><table-wrap-foot><fn id="TFN8"><p id="P84">CHD, coronary heart disease; HDL, high density lipoprotein; LDL, low density lipoprotein; eGFR, estimated glomerular filtration rate; DBP, diastolic blood pressure; SBP systolic blood pressure; PP, pulse pressure; OR, odds ratio; g, grams; INVT, inverse normally transformed (hence no units); N, sample size; <italic>P</italic>, <italic>P</italic>-value of association of BP with the trait listed; CI, confidence interval. Results are considered significant if <italic>P</italic> < 0.0038, which corresponds to a Bonferroni correction for 13 phenotypes tested.</p></fn></table-wrap-foot></table-wrap></floats-group></pmc>
