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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes</title><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="A1">Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.</nlm:aff></affiliation></author><author><name sortKey="Voight, Benjamin F" sort="Voight, Benjamin F" uniqKey="Voight B" first="Benjamin F" last="Voight">Benjamin F. Voight</name><affiliation><nlm:aff id="A2">Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A3">University of Pennsylvania - Perelman School of Medicine, Department of Pharmacology, Philadelphia, Pennsylvania, USA.</nlm:aff></affiliation></author><author><name sortKey="Teslovich, Tanya M" sort="Teslovich, Tanya M" uniqKey="Teslovich T" first="Tanya M" last="Teslovich">Tanya M. Teslovich</name><affiliation><nlm:aff id="A4">Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA.</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="A1">Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.</nlm:aff></affiliation></author><author><name sortKey="Segre, Ayellet V" sort="Segre, Ayellet V" uniqKey="Segre A" first="Ayellet V" last="Segrè">Ayellet V. Segrè</name><affiliation><nlm:aff id="A2">Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A5">Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A6">Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Steinthorsdottir, Valgerdur" sort="Steinthorsdottir, Valgerdur" uniqKey="Steinthorsdottir V" first="Valgerdur" last="Steinthorsdottir">Valgerdur Steinthorsdottir</name><affiliation><nlm:aff id="A7">deCODE Genetics, Reykjavik, Iceland.</nlm:aff></affiliation></author><author><name sortKey="Strawbridge, Rona J" sort="Strawbridge, Rona J" uniqKey="Strawbridge R" first="Rona J" last="Strawbridge">Rona J. Strawbridge</name><affiliation><nlm:aff id="A8">Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.</nlm:aff></affiliation><affiliation><nlm:aff id="A9">Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden.</nlm:aff></affiliation></author><author><name sortKey="Khan, Hassan" sort="Khan, Hassan" uniqKey="Khan H" first="Hassan" last="Khan">Hassan Khan</name><affiliation><nlm:aff id="A10">Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.</nlm:aff></affiliation></author><author><name sortKey="Grallert, Harald" sort="Grallert, Harald" uniqKey="Grallert H" first="Harald" last="Grallert">Harald Grallert</name><affiliation><nlm:aff id="A11">Research Unit of Molecular Epidemiology, Helmholtz Zentrum Muenchen, Neuherberg, Germany.</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="A1">Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.</nlm:aff></affiliation></author><author><name sortKey="Prokopenko, Inga" sort="Prokopenko, Inga" uniqKey="Prokopenko I" first="Inga" last="Prokopenko">Inga Prokopenko</name><affiliation><nlm:aff id="A1">Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.</nlm:aff></affiliation><affiliation><nlm:aff id="A12">Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.</nlm:aff></affiliation></author><author><name sortKey="Kang, Hyun Min" sort="Kang, Hyun Min" uniqKey="Kang H" first="Hyun Min" last="Kang">Hyun Min Kang</name><affiliation><nlm:aff id="A4">Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA.</nlm:aff></affiliation></author><author><name sortKey="Dina, Christian" sort="Dina, Christian" uniqKey="Dina C" first="Christian" last="Dina">Christian Dina</name><affiliation><nlm:aff id="A13">Inserm UMR 1087, Nantes, France.</nlm:aff></affiliation><affiliation><nlm:aff id="A14">CNRS UMR 6291, Nantes, France.</nlm:aff></affiliation><affiliation><nlm:aff id="A15">Nantes University, Nantes, France.</nlm:aff></affiliation></author><author><name sortKey="Esko, Tonu" sort="Esko, Tonu" uniqKey="Esko T" first="Tonu" last="Esko">Tonu Esko</name><affiliation><nlm:aff id="A16">Estonian Genome Center, University of Tartu, Tartu, Estonia.</nlm:aff></affiliation><affiliation><nlm:aff id="A17">Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.</nlm:aff></affiliation></author><author><name sortKey="Fraser, Ross M" sort="Fraser, Ross M" uniqKey="Fraser R" first="Ross M" last="Fraser">Ross M. Fraser</name><affiliation><nlm:aff id="A18">Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK.</nlm:aff></affiliation></author><author><name sortKey="Kanoni, Stavroula" sort="Kanoni, Stavroula" uniqKey="Kanoni S" first="Stavroula" last="Kanoni">Stavroula Kanoni</name><affiliation><nlm:aff id="A19">Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.</nlm:aff></affiliation></author><author><name sortKey="Kumar, Ashish" sort="Kumar, Ashish" uniqKey="Kumar A" first="Ashish" last="Kumar">Ashish Kumar</name><affiliation><nlm:aff id="A1">Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.</nlm:aff></affiliation></author><author><name sortKey="Lagou, Vasiliki" sort="Lagou, Vasiliki" uniqKey="Lagou V" first="Vasiliki" last="Lagou">Vasiliki Lagou</name><affiliation><nlm:aff id="A1">Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, 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="A20">MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.</nlm:aff></affiliation></author><author><name sortKey="Luan, Jian An" sort="Luan, Jian An" uniqKey="Luan J" first="Jian'An" last="Luan">Jian'An Luan</name><affiliation><nlm:aff id="A20">MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, 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="A1">Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.</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="A21">Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany.</nlm:aff></affiliation><affiliation><nlm:aff id="A22">Institute of Genetic Epidemiology, Helmholtz Zentrum Muenchen, Neuherberg, Germany.</nlm:aff></affiliation><affiliation><nlm:aff id="A23">Department of Medicine I, University Hospital Grosshadern, Ludwig-Maximilians-University, Munich, Germany.</nlm:aff></affiliation></author><author><name sortKey="Pechlivanis, Sonali" sort="Pechlivanis, Sonali" uniqKey="Pechlivanis S" first="Sonali" last="Pechlivanis">Sonali Pechlivanis</name><affiliation><nlm:aff id="A24">Institute for Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, University Duisburg-Essen, Essen, Germany.</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="A1">Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.</nlm:aff></affiliation><affiliation><nlm:aff id="A12">Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.</nlm:aff></affiliation></author><author><name sortKey="Scott, Laura J" sort="Scott, Laura J" uniqKey="Scott L" first="Laura J" last="Scott">Laura J. Scott</name><affiliation><nlm:aff id="A4">Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA.</nlm:aff></affiliation></author><author><name sortKey="Wiltshire, Steven" sort="Wiltshire, Steven" uniqKey="Wiltshire S" first="Steven" last="Wiltshire">Steven Wiltshire</name><affiliation><nlm:aff id="A1">Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.</nlm:aff></affiliation></author><author><name sortKey="Yengo, Loic" sort="Yengo, Loic" uniqKey="Yengo L" first="Loic" last="Yengo">Loic Yengo</name><affiliation><nlm:aff id="A25">CNRS-UMR-8199, Institute of Biology and Lille 2 University, Pasteur Institute, Lille, France.</nlm:aff></affiliation><affiliation><nlm:aff id="A26">University Lille 1, Laboratory of Mathematics, CNRS-UMR 8524, MODAL team, INRIA Lille Nord-Europe, Lille, France.</nlm:aff></affiliation></author><author><name sortKey="Kinnunen, Leena" sort="Kinnunen, Leena" uniqKey="Kinnunen L" first="Leena" last="Kinnunen">Leena Kinnunen</name><affiliation><nlm:aff id="A27">Diabetes Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland.</nlm:aff></affiliation></author><author><name sortKey="Rossin, Elizabeth J" sort="Rossin, Elizabeth J" uniqKey="Rossin E" first="Elizabeth J" last="Rossin">Elizabeth J. Rossin</name><affiliation><nlm:aff id="A2">Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A5">Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A28">Health Science and Technology MD Program, Harvard University and Massachusetts Institute of Technology, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A29">Harvard Biological and Biomedical Sciences Program, Harvard University, Boston, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Raychaudhuri, Soumya" sort="Raychaudhuri, Soumya" uniqKey="Raychaudhuri S" first="Soumya" last="Raychaudhuri">Soumya Raychaudhuri</name><affiliation><nlm:aff id="A2">Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A30">Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A31">Partners Center for Personalized Genomic Medicine, Boston, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Johnson, Andrew D" sort="Johnson, Andrew D" uniqKey="Johnson A" first="Andrew D" last="Johnson">Andrew D. Johnson</name><affiliation><nlm:aff id="A32">National Heart, Lung, and Blood Institute’s Framingham Heart Study, Framingham, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Dimas, Antigone S" sort="Dimas, Antigone S" uniqKey="Dimas A" first="Antigone S" last="Dimas">Antigone S. Dimas</name><affiliation><nlm:aff id="A1">Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.</nlm:aff></affiliation><affiliation><nlm:aff id="A33">Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.</nlm:aff></affiliation><affiliation><nlm:aff id="A34">Biomedical Sciences Research Center Al. Fleming, Vari, Greece.</nlm:aff></affiliation></author><author><name sortKey="Loos, Ruth J F" sort="Loos, Ruth J F" uniqKey="Loos R" first="Ruth J F" last="Loos">Ruth J F. Loos</name><affiliation><nlm:aff id="A20">MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.</nlm:aff></affiliation><affiliation><nlm:aff id="A35">Charles R. Bronfman Institute for Personalized Medicine, Mount Sinai School of Medicine, New York, New York, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A36">Child Health and Development Institute, Mount Sinai School of Medicine, New York, New York, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A37">Department of Preventive Medicine, Mount Sinai School of Medicine, New York, New York, USA.</nlm:aff></affiliation></author><author><name sortKey="Vedantam, Sailaja" sort="Vedantam, Sailaja" uniqKey="Vedantam S" first="Sailaja" last="Vedantam">Sailaja Vedantam</name><affiliation><nlm:aff id="A38">Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A39">Division of Genetics and Endocrinology, Children's Hospital, Boston, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Chen, Han" sort="Chen, Han" uniqKey="Chen H" first="Han" last="Chen">Han Chen</name><affiliation><nlm:aff id="A40">Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Florez, Jose C" sort="Florez, Jose C" uniqKey="Florez J" first="Jose C" last="Florez">Jose C. Florez</name><affiliation><nlm:aff id="A5">Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A6">Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A38">Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A41">Diabetes Research Center, Diabetes Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Fox, Caroline" sort="Fox, Caroline" uniqKey="Fox C" first="Caroline" last="Fox">Caroline Fox</name><affiliation><nlm:aff id="A32">National Heart, Lung, and Blood Institute’s Framingham Heart Study, Framingham, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A42">Division of Endocrinology and Metabolism, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Liu, Ching Ti" sort="Liu, Ching Ti" uniqKey="Liu C" first="Ching-Ti" last="Liu">Ching-Ti Liu</name><affiliation><nlm:aff id="A40">Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Rybin, Denis" sort="Rybin, Denis" uniqKey="Rybin D" first="Denis" last="Rybin">Denis Rybin</name><affiliation><nlm:aff id="A43">Boston University Data Coordinating Center, Boston, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Couper, David J" sort="Couper, David J" uniqKey="Couper D" first="David J" last="Couper">David J. Couper</name><affiliation><nlm:aff id="A44">Collaborative Studies Coordinating Center, Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.</nlm:aff></affiliation></author><author><name sortKey="Kao, Wen Hong L" sort="Kao, Wen Hong L" uniqKey="Kao W" first="Wen Hong L" last="Kao">Wen Hong L. Kao</name><affiliation><nlm:aff id="A45">Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.</nlm:aff></affiliation></author><author><name sortKey="Li, Man" sort="Li, Man" uniqKey="Li M" first="Man" last="Li">Man Li</name><affiliation><nlm:aff id="A45">Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.</nlm:aff></affiliation></author><author><name sortKey="Cornelis, Marilyn C" sort="Cornelis, Marilyn C" uniqKey="Cornelis M" first="Marilyn C" last="Cornelis">Marilyn C. Cornelis</name><affiliation><nlm:aff id="A46">Department of Nutrition and Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Kraft, Peter" sort="Kraft, Peter" uniqKey="Kraft P" first="Peter" last="Kraft">Peter Kraft</name><affiliation><nlm:aff id="A46">Department of Nutrition and Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A47">Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Sun, Qi" sort="Sun, Qi" uniqKey="Sun Q" first="Qi" last="Sun">Qi Sun</name><affiliation><nlm:aff id="A46">Department of Nutrition and Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A48">Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Van Dam, Rob M" sort="Van Dam, Rob M" uniqKey="Van Dam R" first="Rob M" last="Van Dam">Rob M. Van Dam</name><affiliation><nlm:aff id="A46">Department of Nutrition and Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A49">Saw Swee Hock School of Public Health, National University of Singapore, Singapore.</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="A4">Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA.</nlm:aff></affiliation></author><author><name sortKey="Chines, Peter S" sort="Chines, Peter S" uniqKey="Chines P" first="Peter S" last="Chines">Peter S. Chines</name><affiliation><nlm:aff id="A50">National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.</nlm:aff></affiliation></author><author><name sortKey="Fischer, Krista" sort="Fischer, Krista" uniqKey="Fischer K" first="Krista" last="Fischer">Krista Fischer</name><affiliation><nlm:aff id="A16">Estonian Genome Center, University of Tartu, Tartu, Estonia.</nlm:aff></affiliation></author><author><name sortKey="Fontanillas, Pierre" sort="Fontanillas, Pierre" uniqKey="Fontanillas P" first="Pierre" last="Fontanillas">Pierre Fontanillas</name><affiliation><nlm:aff id="A2">Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Holmen, Oddgeir L" sort="Holmen, Oddgeir L" uniqKey="Holmen O" first="Oddgeir L" last="Holmen">Oddgeir L. Holmen</name><affiliation><nlm:aff id="A51">HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger, Norway.</nlm:aff></affiliation></author><author><name sortKey="Hunt, Sarah E" sort="Hunt, Sarah E" uniqKey="Hunt S" first="Sarah E" last="Hunt">Sarah E. Hunt</name><affiliation><nlm:aff id="A19">Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.</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="A4">Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA.</nlm:aff></affiliation></author><author><name sortKey="Kong, Augustine" sort="Kong, Augustine" uniqKey="Kong A" first="Augustine" last="Kong">Augustine Kong</name><affiliation><nlm:aff id="A7">deCODE Genetics, Reykjavik, Iceland.</nlm:aff></affiliation></author><author><name sortKey="Lawrence, Robert" sort="Lawrence, Robert" uniqKey="Lawrence R" first="Robert" last="Lawrence">Robert Lawrence</name><affiliation><nlm:aff id="A52">Centre for Genetic Epidemiology and Biostatistics, The University of Western Australia, Nedlands, Australia.</nlm:aff></affiliation></author><author><name sortKey="Meyer, Julia" sort="Meyer, Julia" uniqKey="Meyer J" first="Julia" last="Meyer">Julia Meyer</name><affiliation><nlm:aff id="A22">Institute of Genetic Epidemiology, Helmholtz Zentrum Muenchen, Neuherberg, Germany.</nlm:aff></affiliation></author><author><name sortKey="Perry, John Rb" sort="Perry, John Rb" uniqKey="Perry J" first="John Rb" last="Perry">John Rb Perry</name><affiliation><nlm:aff id="A1">Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.</nlm:aff></affiliation><affiliation><nlm:aff id="A53">Genetics of Complex Traits, Institute of Biomedical and Clinical Science, Peninsula Medical School, University of Exeter, Magdalen Road, Exeter, UK.</nlm:aff></affiliation></author><author><name sortKey="Platou, Carl Gp" sort="Platou, Carl Gp" uniqKey="Platou C" first="Carl Gp" last="Platou">Carl Gp Platou</name><affiliation><nlm:aff id="A51">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="A54">Department of Internal Medicine, Levanger Hospital, Nord-Trøndelag Health Trust, Levanger, Norway.</nlm:aff></affiliation></author><author><name sortKey="Potter, Simon" sort="Potter, Simon" uniqKey="Potter S" first="Simon" last="Potter">Simon Potter</name><affiliation><nlm:aff id="A19">Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.</nlm:aff></affiliation></author><author><name sortKey="Rehnberg, Emil" sort="Rehnberg, Emil" uniqKey="Rehnberg E" first="Emil" last="Rehnberg">Emil Rehnberg</name><affiliation><nlm:aff id="A55">Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.</nlm:aff></affiliation></author><author><name sortKey="Robertson, Neil" sort="Robertson, Neil" uniqKey="Robertson N" first="Neil" last="Robertson">Neil Robertson</name><affiliation><nlm:aff id="A1">Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.</nlm:aff></affiliation><affiliation><nlm:aff id="A12">Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.</nlm:aff></affiliation></author><author><name sortKey="Sivapalaratnam, Suthesh" sort="Sivapalaratnam, Suthesh" uniqKey="Sivapalaratnam S" first="Suthesh" last="Sivapalaratnam">Suthesh Sivapalaratnam</name><affiliation><nlm:aff id="A56">Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.</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="A57">Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.</nlm:aff></affiliation></author><author><name sortKey="Stirrups, Kathleen" sort="Stirrups, Kathleen" uniqKey="Stirrups K" first="Kathleen" last="Stirrups">Kathleen Stirrups</name><affiliation><nlm:aff id="A19">Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.</nlm:aff></affiliation></author><author><name sortKey="Thorleifsson, Gudmar" sort="Thorleifsson, Gudmar" uniqKey="Thorleifsson G" first="Gudmar" last="Thorleifsson">Gudmar Thorleifsson</name><affiliation><nlm:aff id="A7">deCODE Genetics, Reykjavik, Iceland.</nlm:aff></affiliation></author><author><name sortKey="Tikkanen, Emmi" sort="Tikkanen, Emmi" uniqKey="Tikkanen E" first="Emmi" last="Tikkanen">Emmi Tikkanen</name><affiliation><nlm:aff id="A58">Institute for Molecular Medicine Finland (FIMM), Helsinki, Finland.</nlm:aff></affiliation><affiliation><nlm:aff id="A59">Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.</nlm:aff></affiliation></author><author><name sortKey="Wood, Andrew R" sort="Wood, Andrew R" uniqKey="Wood A" first="Andrew R" last="Wood">Andrew R. Wood</name><affiliation><nlm:aff id="A53">Genetics of Complex Traits, Institute of Biomedical and Clinical Science, Peninsula Medical School, University of Exeter, Magdalen Road, Exeter, UK.</nlm:aff></affiliation></author><author><name sortKey="Almgren, Peter" sort="Almgren, Peter" uniqKey="Almgren P" first="Peter" last="Almgren">Peter Almgren</name><affiliation><nlm:aff id="A60">Lund University Diabetes Centre, Department of Clinical Science Malmö, Scania University Hospital, Lund University, Malmö, Sweden.</nlm:aff></affiliation></author><author><name sortKey="Atalay, Mustafa" sort="Atalay, Mustafa" uniqKey="Atalay M" first="Mustafa" last="Atalay">Mustafa Atalay</name><affiliation><nlm:aff id="A61">Institute of Biomedicine, Physiology, University of Eastern Finland, Kuopio Campus, Kuopio, Finland.</nlm:aff></affiliation></author><author><name sortKey="Benediktsson, Rafn" sort="Benediktsson, Rafn" uniqKey="Benediktsson R" first="Rafn" last="Benediktsson">Rafn Benediktsson</name><affiliation><nlm:aff id="A62">Faculty of Medicine, University of Iceland, Reykjavík, Iceland.</nlm:aff></affiliation><affiliation><nlm:aff id="A63">Landspitali University Hospital, Reykjavík, Iceland.</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="A50">National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.</nlm:aff></affiliation></author><author><name sortKey="Burtt, Noel" sort="Burtt, Noel" uniqKey="Burtt N" first="Noël" last="Burtt">Noël Burtt</name><affiliation><nlm:aff id="A2">Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Carey, Jason" sort="Carey, Jason" uniqKey="Carey J" first="Jason" last="Carey">Jason Carey</name><affiliation><nlm:aff id="A2">Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Charpentier, Guillaume" sort="Charpentier, Guillaume" uniqKey="Charpentier G" first="Guillaume" last="Charpentier">Guillaume Charpentier</name><affiliation><nlm:aff id="A64">Endocrinology-Diabetology Unit, Corbeil-Essonnes Hospital, Corbeil-Essonnes, France.</nlm:aff></affiliation></author><author><name sortKey="Crenshaw, Andrew T" sort="Crenshaw, Andrew T" uniqKey="Crenshaw A" first="Andrew T" last="Crenshaw">Andrew T. Crenshaw</name><affiliation><nlm:aff id="A2">Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Doney, Alex S F" sort="Doney, Alex S F" uniqKey="Doney A" first="Alex S F" last="Doney">Alex S F. Doney</name><affiliation><nlm:aff id="A65">Diabetes Research Centre, Biomedical Research Institute, University of Dundee, Ninewells Hospital, Dundee, UK.</nlm:aff></affiliation><affiliation><nlm:aff id="A66">Pharmacogenomics Centre, Biomedical Research Institute, University of Dundee, Ninewells Hospital, Dundee, UK.</nlm:aff></affiliation></author><author><name sortKey="Dorkhan, Mozhgan" sort="Dorkhan, Mozhgan" uniqKey="Dorkhan M" first="Mozhgan" last="Dorkhan">Mozhgan Dorkhan</name><affiliation><nlm:aff id="A60">Lund University Diabetes Centre, Department of Clinical Science Malmö, Scania University Hospital, Lund University, Malmö, Sweden.</nlm:aff></affiliation></author><author><name sortKey="Edkins, Sarah" sort="Edkins, Sarah" uniqKey="Edkins S" first="Sarah" last="Edkins">Sarah Edkins</name><affiliation><nlm:aff id="A19">Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.</nlm:aff></affiliation></author><author><name sortKey="Emilsson, Valur" sort="Emilsson, Valur" uniqKey="Emilsson V" first="Valur" last="Emilsson">Valur Emilsson</name><affiliation><nlm:aff id="A67">Icelandic Heart Association, Kopavogur, Iceland.</nlm:aff></affiliation></author><author><name sortKey="Eury, Elodie" sort="Eury, Elodie" uniqKey="Eury E" first="Elodie" last="Eury">Elodie Eury</name><affiliation><nlm:aff id="A25">CNRS-UMR-8199, Institute of Biology and Lille 2 University, Pasteur Institute, Lille, France.</nlm:aff></affiliation></author><author><name sortKey="Forsen, Tom" sort="Forsen, Tom" uniqKey="Forsen T" first="Tom" last="Forsen">Tom Forsen</name><affiliation><nlm:aff id="A68">Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland.</nlm:aff></affiliation><affiliation><nlm:aff id="A69">Vaasa Health Care Centre, Vaasa, Finland.</nlm:aff></affiliation></author><author><name sortKey="Gertow, Karl" sort="Gertow, Karl" uniqKey="Gertow K" first="Karl" last="Gertow">Karl Gertow</name><affiliation><nlm:aff id="A8">Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.</nlm:aff></affiliation><affiliation><nlm:aff id="A9">Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden.</nlm:aff></affiliation></author><author><name sortKey="Gigante, Bruna" sort="Gigante, Bruna" uniqKey="Gigante B" first="Bruna" last="Gigante">Bruna Gigante</name><affiliation><nlm:aff id="A70">Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.</nlm:aff></affiliation></author><author><name sortKey="Grant, George B" sort="Grant, George B" uniqKey="Grant G" first="George B" last="Grant">George B. Grant</name><affiliation><nlm:aff id="A2">Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, USA.</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="A12">Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.</nlm:aff></affiliation></author><author><name sortKey="Guiducci, Candace" sort="Guiducci, Candace" uniqKey="Guiducci C" first="Candace" last="Guiducci">Candace Guiducci</name><affiliation><nlm:aff id="A2">Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Herder, Christian" sort="Herder, Christian" uniqKey="Herder C" first="Christian" last="Herder">Christian Herder</name><affiliation><nlm:aff id="A71">Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.</nlm:aff></affiliation></author><author><name sortKey="Hreidarsson, Astradur B" sort="Hreidarsson, Astradur B" uniqKey="Hreidarsson A" first="Astradur B" last="Hreidarsson">Astradur B. Hreidarsson</name><affiliation><nlm:aff id="A63">Landspitali University Hospital, Reykjavík, Iceland.</nlm:aff></affiliation></author><author><name sortKey="Hui, Jennie" sort="Hui, Jennie" uniqKey="Hui J" first="Jennie" last="Hui">Jennie Hui</name><affiliation><nlm:aff id="A72">Busselton Population Medical Research Institute, Sir Charles Gairdner Hospital, Nedlands, Australia.</nlm:aff></affiliation><affiliation><nlm:aff id="A73">PathWest Laboratory Medicine of Western Australia, QEII Medical Centre, Nedlands, Australia.</nlm:aff></affiliation><affiliation><nlm:aff id="A74">School of Pathology and Laboratory Medicine, The University of Western Australia, Nedlands, Australia.</nlm:aff></affiliation><affiliation><nlm:aff id="A75">School of Population Health, The University of Western Australia, Nedlands, Australia.</nlm:aff></affiliation></author><author><name sortKey="James, Alan" sort="James, Alan" uniqKey="James A" first="Alan" last="James">Alan James</name><affiliation><nlm:aff id="A72">Busselton Population Medical Research Institute, Sir Charles Gairdner Hospital, Nedlands, Australia.</nlm:aff></affiliation><affiliation><nlm:aff id="A76">Department of Pulmonary Physiology and Sleep Medicine, West Australian Sleep Disorders Research Institute, Queen Elizabeth II Medical Centre, Hospital Avenue, Nedlands, Australia.</nlm:aff></affiliation><affiliation><nlm:aff id="A77">School of Medicine and Pharmacology, University of Western Australia, Nedlands, Australia.</nlm:aff></affiliation></author><author><name sortKey="Jonsson, Anna" sort="Jonsson, Anna" uniqKey="Jonsson A" first="Anna" last="Jonsson">Anna Jonsson</name><affiliation><nlm:aff id="A60">Lund University Diabetes Centre, Department of Clinical Science Malmö, Scania University Hospital, Lund University, Malmö, Sweden.</nlm:aff></affiliation></author><author><name sortKey="Rathmann, Wolfgang" sort="Rathmann, Wolfgang" uniqKey="Rathmann W" first="Wolfgang" last="Rathmann">Wolfgang Rathmann</name><affiliation><nlm:aff id="A78">Institute of Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.</nlm:aff></affiliation></author><author><name sortKey="Klopp, Norman" sort="Klopp, Norman" uniqKey="Klopp N" first="Norman" last="Klopp">Norman Klopp</name><affiliation><nlm:aff id="A11">Research Unit of Molecular Epidemiology, Helmholtz Zentrum Muenchen, Neuherberg, Germany.</nlm:aff></affiliation></author><author><name sortKey="Kravic, Jasmina" sort="Kravic, Jasmina" uniqKey="Kravic J" first="Jasmina" last="Kravic">Jasmina Kravic</name><affiliation><nlm:aff id="A60">Lund University Diabetes Centre, Department of Clinical Science Malmö, Scania University Hospital, Lund University, Malmö, Sweden.</nlm:aff></affiliation></author><author><name sortKey="Krjutskov, Kaarel" sort="Krjutskov, Kaarel" uniqKey="Krjutskov K" first="Kaarel" last="Krjutškov">Kaarel Krjutškov</name><affiliation><nlm:aff id="A16">Estonian Genome Center, University of Tartu, Tartu, Estonia.</nlm:aff></affiliation></author><author><name sortKey="Langford, Cordelia" sort="Langford, Cordelia" uniqKey="Langford C" first="Cordelia" last="Langford">Cordelia Langford</name><affiliation><nlm:aff id="A19">Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.</nlm:aff></affiliation></author><author><name sortKey="Leander, Karin" sort="Leander, Karin" uniqKey="Leander K" first="Karin" last="Leander">Karin Leander</name><affiliation><nlm:aff id="A70">Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.</nlm:aff></affiliation></author><author><name sortKey="Lindholm, Eero" sort="Lindholm, Eero" uniqKey="Lindholm E" first="Eero" last="Lindholm">Eero Lindholm</name><affiliation><nlm:aff id="A60">Lund University Diabetes Centre, Department of Clinical Science Malmö, Scania University Hospital, Lund University, Malmö, Sweden.</nlm:aff></affiliation></author><author><name sortKey="Lobbens, Stephane" sort="Lobbens, Stephane" uniqKey="Lobbens S" first="Stéphane" last="Lobbens">Stéphane Lobbens</name><affiliation><nlm:aff id="A25">CNRS-UMR-8199, Institute of Biology and Lille 2 University, Pasteur Institute, Lille, France.</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="A59">Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.</nlm:aff></affiliation></author><author><name sortKey="Mirza, Ghazala" sort="Mirza, Ghazala" uniqKey="Mirza G" first="Ghazala" last="Mirza">Ghazala Mirza</name><affiliation><nlm:aff id="A1">Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.</nlm:aff></affiliation></author><author><name sortKey="Muhleisen, Thomas W" sort="Muhleisen, Thomas W" uniqKey="Muhleisen T" first="Thomas W" last="Mühleisen">Thomas W. Mühleisen</name><affiliation><nlm:aff id="A79">Institute of Human Genetics, University of Bonn, Bonn, Germany.</nlm:aff></affiliation><affiliation><nlm:aff id="A80">Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.</nlm:aff></affiliation></author><author><name sortKey="Musk, Bill" sort="Musk, Bill" uniqKey="Musk B" first="Bill" last="Musk">Bill Musk</name><affiliation><nlm:aff id="A72">Busselton Population Medical Research Institute, Sir Charles Gairdner Hospital, Nedlands, Australia.</nlm:aff></affiliation><affiliation><nlm:aff id="A75">School of Population Health, The University of Western Australia, Nedlands, Australia.</nlm:aff></affiliation><affiliation><nlm:aff id="A77">School of Medicine and Pharmacology, University of Western Australia, Nedlands, Australia.</nlm:aff></affiliation><affiliation><nlm:aff id="A81">Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, Australia.</nlm:aff></affiliation></author><author><name sortKey="Parkin, Melissa" sort="Parkin, Melissa" uniqKey="Parkin M" first="Melissa" last="Parkin">Melissa Parkin</name><affiliation><nlm:aff id="A2">Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Rallidis, Loukianos" sort="Rallidis, Loukianos" uniqKey="Rallidis L" first="Loukianos" last="Rallidis">Loukianos Rallidis</name><affiliation><nlm:aff id="A82">University General Hospital Attikon, Athens, Greece.</nlm:aff></affiliation></author><author><name sortKey="Saramies, Jouko" sort="Saramies, Jouko" uniqKey="Saramies J" first="Jouko" last="Saramies">Jouko Saramies</name><affiliation><nlm:aff id="A83">South Karelia Central Hospital, Lappeenranta, Finland.</nlm:aff></affiliation></author><author><name sortKey="Sennblad, Bengt" sort="Sennblad, Bengt" uniqKey="Sennblad B" first="Bengt" last="Sennblad">Bengt Sennblad</name><affiliation><nlm:aff id="A8">Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.</nlm:aff></affiliation><affiliation><nlm:aff id="A9">Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden.</nlm:aff></affiliation></author><author><name sortKey="Shah, Sonia" sort="Shah, Sonia" uniqKey="Shah S" first="Sonia" last="Shah">Sonia Shah</name><affiliation><nlm:aff id="A84">UCL Genetics Institute, Department of Genetics, Evolution and Environment, University College London, London, UK.</nlm:aff></affiliation></author><author><name sortKey="Sigur Sson, Gunnar" sort="Sigur Sson, Gunnar" uniqKey="Sigur Sson G" first="Gunnar" last="Sigur Sson">Gunnar Sigur Sson</name><affiliation><nlm:aff id="A63">Landspitali University Hospital, Reykjavík, Iceland.</nlm:aff></affiliation><affiliation><nlm:aff id="A67">Icelandic Heart Association, Kopavogur, Iceland.</nlm:aff></affiliation></author><author><name sortKey="Silveira, Angela" sort="Silveira, Angela" uniqKey="Silveira A" first="Angela" last="Silveira">Angela Silveira</name><affiliation><nlm:aff id="A8">Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.</nlm:aff></affiliation><affiliation><nlm:aff id="A9">Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden.</nlm:aff></affiliation></author><author><name sortKey="Steinbach, Gerald" sort="Steinbach, Gerald" uniqKey="Steinbach G" first="Gerald" last="Steinbach">Gerald Steinbach</name><affiliation><nlm:aff id="A85">Department of Clinical Chemistry and Central Laboratory, University of Ulm, Ulm, Germany.</nlm:aff></affiliation></author><author><name sortKey="Thorand, Barbara" sort="Thorand, Barbara" uniqKey="Thorand B" first="Barbara" last="Thorand">Barbara Thorand</name><affiliation><nlm:aff id="A86">Institute of Epidemiology II, Helmholtz Zentrum Muenchen, Neuherberg, Germany.</nlm:aff></affiliation></author><author><name sortKey="Trakalo, Joseph" sort="Trakalo, Joseph" uniqKey="Trakalo J" first="Joseph" last="Trakalo">Joseph Trakalo</name><affiliation><nlm:aff id="A1">Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.</nlm:aff></affiliation></author><author><name sortKey="Veglia, Fabrizio" sort="Veglia, Fabrizio" uniqKey="Veglia F" first="Fabrizio" last="Veglia">Fabrizio Veglia</name><affiliation><nlm:aff id="A87">Centro Cardiologico Monzino, IRCCS, Milan, Italy.</nlm:aff></affiliation></author><author><name sortKey="Wennauer, Roman" sort="Wennauer, Roman" uniqKey="Wennauer R" first="Roman" last="Wennauer">Roman Wennauer</name><affiliation><nlm:aff id="A85">Department of Clinical Chemistry and Central Laboratory, University of Ulm, Ulm, Germany.</nlm:aff></affiliation></author><author><name sortKey="Winckler, Wendy" sort="Winckler, Wendy" uniqKey="Winckler W" first="Wendy" last="Winckler">Wendy Winckler</name><affiliation><nlm:aff id="A2">Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Zabaneh, Delilah" sort="Zabaneh, Delilah" uniqKey="Zabaneh D" first="Delilah" last="Zabaneh">Delilah Zabaneh</name><affiliation><nlm:aff id="A84">UCL Genetics Institute, Department of Genetics, Evolution and Environment, University College London, London, UK.</nlm:aff></affiliation></author><author><name sortKey="Campbell, Harry" sort="Campbell, Harry" uniqKey="Campbell H" first="Harry" last="Campbell">Harry Campbell</name><affiliation><nlm:aff id="A18">Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK.</nlm:aff></affiliation><affiliation><nlm:aff id="A88">MRC Institute of Genetics and Molecular Medicine at the University of Edinburgh, Western General Hospital, Edinburgh, UK.</nlm:aff></affiliation></author><author><name sortKey="Van Duijn, Cornelia" sort="Van Duijn, Cornelia" uniqKey="Van Duijn C" first="Cornelia" last="Van Duijn">Cornelia Van Duijn</name><affiliation><nlm:aff id="A89">Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.</nlm:aff></affiliation><affiliation><nlm:aff id="A90">Netherland Genomics Initiative, Netherlands Consortium for Healthy Ageing and Centre for Medical Systems Biology, Rotterdam, The Netherlands.</nlm:aff></affiliation></author><author><name sortKey="Uitterlinden89, Andre G" sort="Uitterlinden89, Andre G" uniqKey="Uitterlinden89 A" first="Andre G" last="Uitterlinden89-">Andre G. Uitterlinden89-</name><affiliation><nlm:aff id="A89">Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.</nlm:aff></affiliation><affiliation><nlm:aff id="A90">Netherland Genomics Initiative, Netherlands Consortium for Healthy Ageing and Centre for Medical Systems Biology, Rotterdam, The Netherlands.</nlm:aff></affiliation><affiliation><nlm:aff id="A91">Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.</nlm:aff></affiliation></author><author><name sortKey="Hofman, Albert" sort="Hofman, Albert" uniqKey="Hofman A" first="Albert" last="Hofman">Albert Hofman</name><affiliation><nlm:aff id="A89">Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.</nlm:aff></affiliation></author><author><name sortKey="Sijbrands, Eric" sort="Sijbrands, Eric" uniqKey="Sijbrands E" first="Eric" last="Sijbrands">Eric Sijbrands</name><affiliation><nlm:aff id="A91">Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.</nlm:aff></affiliation></author><author><name sortKey="Abecasis, Goncalo R" sort="Abecasis, Goncalo R" uniqKey="Abecasis G" first="Goncalo R" last="Abecasis">Goncalo R. Abecasis</name><affiliation><nlm:aff id="A4">Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA.</nlm:aff></affiliation></author><author><name sortKey="Owen, Katharine R" sort="Owen, Katharine R" uniqKey="Owen K" first="Katharine R" last="Owen">Katharine R. Owen</name><affiliation><nlm:aff id="A12">Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.</nlm:aff></affiliation><affiliation><nlm:aff id="A92">Oxford National Institute for Health Research Biomedical Research Centre, Churchill Hospital, Oxford, 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="A19">Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.</nlm:aff></affiliation></author><author><name sortKey="Trip, Mieke D" sort="Trip, Mieke D" uniqKey="Trip M" first="Mieke D" last="Trip">Mieke D. Trip</name><affiliation><nlm:aff id="A56">Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.</nlm:aff></affiliation></author><author><name sortKey="Forouhi, Nita G" sort="Forouhi, Nita G" uniqKey="Forouhi N" first="Nita G" last="Forouhi">Nita G. Forouhi</name><affiliation><nlm:aff id="A20">MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.</nlm:aff></affiliation></author><author><name sortKey="Syv Nen, Ann Christine" sort="Syv Nen, Ann Christine" uniqKey="Syv Nen A" first="Ann-Christine" last="Syv Nen">Ann-Christine Syv Nen</name><affiliation><nlm:aff id="A93">Molecular Medicine, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.</nlm:aff></affiliation></author><author><name sortKey="Eriksson, Johan G" sort="Eriksson, Johan G" uniqKey="Eriksson J" first="Johan G" last="Eriksson">Johan G. Eriksson</name><affiliation><nlm:aff id="A59">Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.</nlm:aff></affiliation><affiliation><nlm:aff id="A68">Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland.</nlm:aff></affiliation><affiliation><nlm:aff id="A94">Unit of General Practice, Helsinki University General Hospital, Helsinki, Finland.</nlm:aff></affiliation><affiliation><nlm:aff id="A95">Folkhälsan Research Center, Helsinki, Finland.</nlm:aff></affiliation></author><author><name sortKey="Peltonen, Leena" sort="Peltonen, Leena" uniqKey="Peltonen L" first="Leena" last="Peltonen">Leena Peltonen</name><affiliation><nlm:aff id="A2">Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A19">Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.</nlm:aff></affiliation><affiliation><nlm:aff id="A58">Institute for Molecular Medicine Finland (FIMM), Helsinki, Finland.</nlm:aff></affiliation><affiliation><nlm:aff id="A59">Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.</nlm:aff></affiliation></author><author><name sortKey="Nothen, Markus M" sort="Nothen, Markus M" uniqKey="Nothen M" first="Markus M" last="Nöthen">Markus M. Nöthen</name><affiliation><nlm:aff id="A79">Institute of Human Genetics, University of Bonn, Bonn, Germany.</nlm:aff></affiliation><affiliation><nlm:aff id="A80">Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.</nlm:aff></affiliation></author><author><name sortKey="Balkau, Beverley" sort="Balkau, Beverley" uniqKey="Balkau B" first="Beverley" last="Balkau">Beverley Balkau</name><affiliation><nlm:aff id="A96">INSERM CESP U1018, Villejuif, France.</nlm:aff></affiliation><affiliation><nlm:aff id="A97">University Paris Sud 11, UMRS 1018, Villejuif, France.</nlm:aff></affiliation></author><author><name sortKey="Palmer, Colin N A" sort="Palmer, Colin N A" uniqKey="Palmer C" first="Colin N A" last="Palmer">Colin N A. Palmer</name><affiliation><nlm:aff id="A65">Diabetes Research Centre, Biomedical Research Institute, University of Dundee, Ninewells Hospital, Dundee, UK.</nlm:aff></affiliation><affiliation><nlm:aff id="A66">Pharmacogenomics Centre, Biomedical Research Institute, University of Dundee, Ninewells Hospital, Dundee, UK.</nlm:aff></affiliation></author><author><name sortKey="Lyssenko, Valeriya" sort="Lyssenko, Valeriya" uniqKey="Lyssenko V" first="Valeriya" last="Lyssenko">Valeriya Lyssenko</name><affiliation><nlm:aff id="A60">Lund University Diabetes Centre, Department of Clinical Science Malmö, Scania University Hospital, Lund University, Malmö, Sweden.</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="A95">Folkhälsan Research Center, Helsinki, Finland.</nlm:aff></affiliation><affiliation><nlm:aff id="A98">Department of Medicine, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.</nlm:aff></affiliation></author><author><name sortKey="Isomaa, Bo" sort="Isomaa, Bo" uniqKey="Isomaa B" first="Bo" last="Isomaa">Bo Isomaa</name><affiliation><nlm:aff id="A95">Folkhälsan Research Center, Helsinki, Finland.</nlm:aff></affiliation><affiliation><nlm:aff id="A99">Department of Social Services and Health Care, Jakobstad, Finland.</nlm:aff></affiliation></author><author><name sortKey="Hunter, David J" sort="Hunter, David J" uniqKey="Hunter D" first="David J" last="Hunter">David J. Hunter</name><affiliation><nlm:aff id="A46">Department of Nutrition and Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A47">Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A48">Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Qi, Lu" sort="Qi, Lu" uniqKey="Qi L" first="Lu" last="Qi">Lu Qi</name><affiliation><nlm:aff id="A46">Department of Nutrition and Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A48">Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Shuldiner, Alan R" sort="Shuldiner, Alan R" uniqKey="Shuldiner A" first="Alan R" last="Shuldiner">Alan R. Shuldiner</name><affiliation><nlm:aff id="A100">Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A101">Geriatric Research Education and Clinical Center, Baltimore Veterans Administration Medical Center, Baltimore, Maryland, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A102">Program in Personalised and Genomic Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.</nlm:aff></affiliation></author><author><name sortKey="Roden, Michael" sort="Roden, Michael" uniqKey="Roden M" first="Michael" last="Roden">Michael Roden</name><affiliation><nlm:aff id="A71">Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.</nlm:aff></affiliation><affiliation><nlm:aff id="A103">Department of Medicine/Metabolic Diseases, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.</nlm:aff></affiliation></author><author><name sortKey="Barroso, Ines" sort="Barroso, Ines" uniqKey="Barroso I" first="Ines" last="Barroso">Ines Barroso</name><affiliation><nlm:aff id="A19">Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.</nlm:aff></affiliation><affiliation><nlm:aff id="A104">University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge, UK.</nlm:aff></affiliation><affiliation><nlm:aff id="A105">NIHR Cambridge Biomedical Research Centre, Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge, UK.</nlm:aff></affiliation></author><author><name sortKey="Wilsgaard, Tom" sort="Wilsgaard, Tom" uniqKey="Wilsgaard T" first="Tom" last="Wilsgaard">Tom Wilsgaard</name><affiliation><nlm:aff id="A106">Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway.</nlm:aff></affiliation></author><author><name sortKey="Beilby, John" sort="Beilby, John" uniqKey="Beilby J" first="John" last="Beilby">John Beilby</name><affiliation><nlm:aff id="A72">Busselton Population Medical Research Institute, Sir Charles Gairdner Hospital, Nedlands, Australia.</nlm:aff></affiliation><affiliation><nlm:aff id="A73">PathWest Laboratory Medicine of Western Australia, QEII Medical Centre, Nedlands, Australia.</nlm:aff></affiliation><affiliation><nlm:aff id="A74">School of Pathology and Laboratory Medicine, The University of Western Australia, Nedlands, Australia.</nlm:aff></affiliation></author><author><name sortKey="Hovingh, Kees" sort="Hovingh, Kees" uniqKey="Hovingh K" first="Kees" last="Hovingh">Kees Hovingh</name><affiliation><nlm:aff id="A56">Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.</nlm:aff></affiliation></author><author><name sortKey="Price, Jackie F" sort="Price, Jackie F" uniqKey="Price J" first="Jackie F" last="Price">Jackie F. Price</name><affiliation><nlm:aff id="A18">Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK.</nlm:aff></affiliation></author><author><name sortKey="Wilson, James F" sort="Wilson, James F" uniqKey="Wilson J" first="James F" last="Wilson">James F. Wilson</name><affiliation><nlm:aff id="A18">Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK.</nlm:aff></affiliation><affiliation><nlm:aff id="A88">MRC Institute of Genetics and Molecular Medicine at the University of Edinburgh, Western General Hospital, Edinburgh, UK.</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="A107">Kuopio Research Institute of Exercise Medicine, Kuopio, Finland.</nlm:aff></affiliation><affiliation><nlm:aff id="A108">Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, 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="A61">Institute of Biomedicine, Physiology, University of Eastern Finland, Kuopio Campus, Kuopio, Finland.</nlm:aff></affiliation><affiliation><nlm:aff id="A107">Kuopio Research Institute of Exercise Medicine, Kuopio, Finland.</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="A109">Department of Medical Sciences, Uppsala University, Akademiska Sjukhuset, Uppsala, Sweden.</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="A110">Department of Dietetics-Nutrition, Harokopio University, Athens, Greece.</nlm:aff></affiliation></author><author><name sortKey="Nj Lstad, Inger" sort="Nj Lstad, Inger" uniqKey="Nj Lstad I" first="Inger" last="Nj Lstad">Inger Nj Lstad</name><affiliation><nlm:aff id="A106">Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway.</nlm:aff></affiliation></author><author><name sortKey="Pedersen, Nancy L" sort="Pedersen, Nancy L" uniqKey="Pedersen N" first="Nancy L" last="Pedersen">Nancy L. Pedersen</name><affiliation><nlm:aff id="A55">Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.</nlm:aff></affiliation></author><author><name sortKey="Khaw, Kay Tee" sort="Khaw, Kay Tee" uniqKey="Khaw K" first="Kay-Tee" last="Khaw">Kay-Tee Khaw</name><affiliation><nlm:aff id="A10">Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.</nlm:aff></affiliation></author><author><name sortKey="Wareham, Nicholas J" sort="Wareham, Nicholas J" uniqKey="Wareham N" first="Nicholas J" last="Wareham">Nicholas J. Wareham</name><affiliation><nlm:aff id="A20">MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.</nlm:aff></affiliation></author><author><name sortKey="Keinanen Kiukaanniemi, Sirkka M" sort="Keinanen Kiukaanniemi, Sirkka M" uniqKey="Keinanen Kiukaanniemi S" first="Sirkka M" last="Keinanen-Kiukaanniemi">Sirkka M. Keinanen-Kiukaanniemi</name><affiliation><nlm:aff id="A111">Faculty of Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland.</nlm:aff></affiliation><affiliation><nlm:aff id="A112">Unit of General Practice, Oulu University Hospital, Oulu, Finland.</nlm:aff></affiliation></author><author><name sortKey="Saaristo, Timo E" sort="Saaristo, Timo E" uniqKey="Saaristo T" first="Timo E" last="Saaristo">Timo E. Saaristo</name><affiliation><nlm:aff id="A113">Finnish Diabetes Association, Tampere, Finland.</nlm:aff></affiliation><affiliation><nlm:aff id="A114">Pirkanmaa Hospital District, Tampere, Finland.</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="A115">South Ostrobothnia Central Hospital, Seinäjoki, Finland.</nlm:aff></affiliation></author><author><name sortKey="Saltevo, Juha" sort="Saltevo, Juha" uniqKey="Saltevo J" first="Juha" last="Saltevo">Juha Saltevo</name><affiliation><nlm:aff id="A116">Department of Medicine, Central Finland Central Hospital, Jyväskylä, 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="A57">Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.</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="A57">Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.</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="A16">Estonian Genome Center, University of Tartu, Tartu, Estonia.</nlm:aff></affiliation><affiliation><nlm:aff id="A17">Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.</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="A50">National Human Genome Research Institute, National Institutes of Health, 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="A117">Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA.</nlm:aff></affiliation></author><author><name sortKey="Bergman, Richard N" sort="Bergman, Richard N" uniqKey="Bergman R" first="Richard N" last="Bergman">Richard N. Bergman</name><affiliation><nlm:aff id="A118">Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.</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="A27">Diabetes Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland.</nlm:aff></affiliation><affiliation><nlm:aff id="A115">South Ostrobothnia Central Hospital, Seinäjoki, Finland.</nlm:aff></affiliation><affiliation><nlm:aff id="A119">Red RECAVA Grupo RD06/0014/0015, Hospital Universitario La Paz, Madrid, Spain.</nlm:aff></affiliation><affiliation><nlm:aff id="A120">Centre for Vascular Prevention, Danube-University Krems, Krems, Austria.</nlm:aff></affiliation></author><author><name sortKey="Boehm, Bernhard O" sort="Boehm, Bernhard O" uniqKey="Boehm B" first="Bernhard O" last="Boehm">Bernhard O. Boehm</name><affiliation><nlm:aff id="A121">Division of Endocrinology and Diabetes, Department of Internal Medicine, University Medical Centre Ulm, Ulm, Germany.</nlm:aff></affiliation></author><author><name sortKey="Gieger, Christian" sort="Gieger, Christian" uniqKey="Gieger C" first="Christian" last="Gieger">Christian Gieger</name><affiliation><nlm:aff id="A22">Institute of Genetic Epidemiology, Helmholtz Zentrum Muenchen, Neuherberg, Germany.</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="A51">HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger, Norway.</nlm:aff></affiliation></author><author><name sortKey="Cauchi, Stephane" sort="Cauchi, Stephane" uniqKey="Cauchi S" first="Stephane" last="Cauchi">Stephane Cauchi</name><affiliation><nlm:aff id="A25">CNRS-UMR-8199, Institute of Biology and Lille 2 University, Pasteur Institute, Lille, France.</nlm:aff></affiliation></author><author><name sortKey="Froguel, Philippe" sort="Froguel, Philippe" uniqKey="Froguel P" first="Philippe" last="Froguel">Philippe Froguel</name><affiliation><nlm:aff id="A25">CNRS-UMR-8199, Institute of Biology and Lille 2 University, Pasteur Institute, Lille, France.</nlm:aff></affiliation><affiliation><nlm:aff id="A122">Genomic Medicine, Imperial College London, Hammersmith Hospital, London, UK.</nlm:aff></affiliation></author><author><name sortKey="Baldassarre, Damiano" sort="Baldassarre, Damiano" uniqKey="Baldassarre D" first="Damiano" last="Baldassarre">Damiano Baldassarre</name><affiliation><nlm:aff id="A87">Centro Cardiologico Monzino, IRCCS, Milan, Italy.</nlm:aff></affiliation><affiliation><nlm:aff id="A123">Department of Pharmacological Sciences, University of Milan, Milan, Italy.</nlm:aff></affiliation></author><author><name sortKey="Tremoli, Elena" sort="Tremoli, Elena" uniqKey="Tremoli E" first="Elena" last="Tremoli">Elena Tremoli</name><affiliation><nlm:aff id="A87">Centro Cardiologico Monzino, IRCCS, Milan, Italy.</nlm:aff></affiliation><affiliation><nlm:aff id="A123">Department of Pharmacological Sciences, University of Milan, Milan, Italy.</nlm:aff></affiliation></author><author><name sortKey="Humphries, Steve E" sort="Humphries, Steve E" uniqKey="Humphries S" first="Steve E" last="Humphries">Steve E. Humphries</name><affiliation><nlm:aff id="A124">Institute of Cardiovascular Science, University College London, London, 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="A10">Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.</nlm:aff></affiliation><affiliation><nlm:aff id="A125">Center for Non-Communicable Diseases Pakistan, Karachi, Pakistan.</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="A10">Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.</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="A55">Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.</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="A19">Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.</nlm:aff></affiliation><affiliation><nlm:aff id="A58">Institute for Molecular Medicine Finland (FIMM), Helsinki, Finland.</nlm:aff></affiliation><affiliation><nlm:aff id="A59">Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.</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="A59">Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.</nlm:aff></affiliation></author><author><name sortKey="Erbel, Raimund" sort="Erbel, Raimund" uniqKey="Erbel R" first="Raimund" last="Erbel">Raimund Erbel</name><affiliation><nlm:aff id="A126">Clinic of Cardiology, West German Heart Centre, University Hospital of Essen, University Duisburg-Essen, Essen, Germany.</nlm:aff></affiliation></author><author><name sortKey="Jockel, Karl Heinz" sort="Jockel, Karl Heinz" uniqKey="Jockel K" first="Karl-Heinz" last="Jöckel">Karl-Heinz Jöckel</name><affiliation><nlm:aff id="A24">Institute for Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, University Duisburg-Essen, Essen, Germany.</nlm:aff></affiliation></author><author><name sortKey="Moebus, Susanne" sort="Moebus, Susanne" uniqKey="Moebus S" first="Susanne" last="Moebus">Susanne Moebus</name><affiliation><nlm:aff id="A24">Institute for Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, University Duisburg-Essen, Essen, Germany.</nlm:aff></affiliation></author><author><name sortKey="Peters, Annette" sort="Peters, Annette" uniqKey="Peters A" first="Annette" last="Peters">Annette Peters</name><affiliation><nlm:aff id="A86">Institute of Epidemiology II, Helmholtz Zentrum Muenchen, Neuherberg, Germany.</nlm:aff></affiliation></author><author><name sortKey="Illig, Thomas" sort="Illig, Thomas" uniqKey="Illig T" first="Thomas" last="Illig">Thomas Illig</name><affiliation><nlm:aff id="A11">Research Unit of Molecular Epidemiology, Helmholtz Zentrum Muenchen, Neuherberg, Germany.</nlm:aff></affiliation><affiliation><nlm:aff id="A127">Hannover Unified Biobank, Hannover Medical School, Hannover, Germany.</nlm:aff></affiliation></author><author><name sortKey="De Faire, Ulf" sort="De Faire, Ulf" uniqKey="De Faire U" first="Ulf" last="De Faire">Ulf De Faire</name><affiliation><nlm:aff id="A70">Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.</nlm:aff></affiliation></author><author><name sortKey="Hamsten, Anders" sort="Hamsten, Anders" uniqKey="Hamsten A" first="Anders" last="Hamsten">Anders Hamsten</name><affiliation><nlm:aff id="A8">Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.</nlm:aff></affiliation><affiliation><nlm:aff id="A9">Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden.</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="A65">Diabetes Research Centre, Biomedical Research Institute, University of Dundee, Ninewells Hospital, Dundee, UK.</nlm:aff></affiliation><affiliation><nlm:aff id="A66">Pharmacogenomics Centre, Biomedical Research Institute, University of Dundee, Ninewells Hospital, Dundee, UK.</nlm:aff></affiliation></author><author><name sortKey="Donnelly, Peter J" sort="Donnelly, Peter J" uniqKey="Donnelly P" first="Peter J" last="Donnelly">Peter J. Donnelly</name><affiliation><nlm:aff id="A1">Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.</nlm:aff></affiliation><affiliation><nlm:aff id="A128">Department of Statistics, University of Oxford, Oxford, UK.</nlm:aff></affiliation></author><author><name sortKey="Frayling, Timothy M" sort="Frayling, Timothy M" uniqKey="Frayling T" first="Timothy M" last="Frayling">Timothy M. Frayling</name><affiliation><nlm:aff id="A53">Genetics of Complex Traits, Institute of Biomedical and Clinical Science, Peninsula Medical School, University of Exeter, Magdalen Road, Exeter, UK.</nlm:aff></affiliation></author><author><name sortKey="Hattersley, Andrew T" sort="Hattersley, Andrew T" uniqKey="Hattersley A" first="Andrew T" last="Hattersley">Andrew T. Hattersley</name><affiliation><nlm:aff id="A129">Diabetes Genetics, Institute of Biomedical and Clinical Science, Peninsula Medical School, University of Exeter, Exeter, UK.</nlm:aff></affiliation></author><author><name sortKey="Boerwinkle, Eric" sort="Boerwinkle, Eric" uniqKey="Boerwinkle E" first="Eric" last="Boerwinkle">Eric Boerwinkle</name><affiliation><nlm:aff id="A130">Human Genetics Center, University of Texas Health Science Center at Houston, Houston, Texas, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A131">Human Genome Sequencing Center at Baylor College of Medicine, Houston, Texas, 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="A60">Lund University Diabetes Centre, Department of Clinical Science Malmö, Scania University Hospital, Lund University, Malmö, Sweden.</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="A2">Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A5">Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A132">Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Nilsson, Peter M" sort="Nilsson, Peter M" uniqKey="Nilsson P" first="Peter M" last="Nilsson">Peter M. Nilsson</name><affiliation><nlm:aff id="A60">Lund University Diabetes Centre, Department of Clinical Science Malmö, Scania University Hospital, Lund University, Malmö, Sweden.</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="A19">Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.</nlm:aff></affiliation></author><author><name sortKey="Thorsteinsdottir, Unnur" sort="Thorsteinsdottir, Unnur" uniqKey="Thorsteinsdottir U" first="Unnur" last="Thorsteinsdottir">Unnur Thorsteinsdottir</name><affiliation><nlm:aff id="A7">deCODE Genetics, Reykjavik, Iceland.</nlm:aff></affiliation><affiliation><nlm:aff id="A62">Faculty of Medicine, University of Iceland, Reykjavík, Iceland.</nlm:aff></affiliation></author><author><name sortKey="Groop, Leif C" sort="Groop, Leif C" uniqKey="Groop L" first="Leif C" last="Groop">Leif C. Groop</name><affiliation><nlm:aff id="A60">Lund University Diabetes Centre, Department of Clinical Science Malmö, Scania University Hospital, Lund University, Malmö, Sweden.</nlm:aff></affiliation></author><author><name sortKey="Stefansson, Kari" sort="Stefansson, Kari" uniqKey="Stefansson K" first="Kari" last="Stefansson">Kari Stefansson</name><affiliation><nlm:aff id="A7">deCODE Genetics, Reykjavik, Iceland.</nlm:aff></affiliation><affiliation><nlm:aff id="A62">Faculty of Medicine, University of Iceland, Reykjavík, Iceland.</nlm:aff></affiliation></author><author><name sortKey="Hu, Frank" sort="Hu, Frank" uniqKey="Hu F" first="Frank" last="Hu">Frank Hu</name><affiliation><nlm:aff id="A46">Department of Nutrition and Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A48">Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Pankow, James S" sort="Pankow, James S" uniqKey="Pankow J" first="James S" last="Pankow">James S. Pankow</name><affiliation><nlm:aff id="A133">Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, Minnesota, USA.</nlm:aff></affiliation></author><author><name sortKey="Dupuis, Josee" sort="Dupuis, Josee" uniqKey="Dupuis J" first="Josée" last="Dupuis">Josée Dupuis</name><affiliation><nlm:aff id="A32">National Heart, Lung, and Blood Institute’s Framingham Heart Study, Framingham, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A40">Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Meigs, James B" sort="Meigs, James B" uniqKey="Meigs J" first="James B" last="Meigs">James B. Meigs</name><affiliation><nlm:aff id="A6">Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A134">General Medicine Division, Massachusetts General Hospital, Boston, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Altshuler, David" sort="Altshuler, David" uniqKey="Altshuler D" first="David" last="Altshuler">David Altshuler</name><affiliation><nlm:aff id="A2">Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A5">Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A6">Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A135">Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A136">Department of Molecular Biology, Harvard Medical School, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A137">Diabetes Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.</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="A4">Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA.</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="A1">Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.</nlm:aff></affiliation><affiliation><nlm:aff id="A12">Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.</nlm:aff></affiliation><affiliation><nlm:aff id="A92">Oxford National Institute for Health Research Biomedical Research Centre, Churchill Hospital, Oxford, UK.</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">22885922</idno><idno type="pmc">3442244</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3442244</idno><idno type="RBID">PMC:3442244</idno><idno type="doi">10.1038/ng.2383</idno><date when="2012">2012</date><idno type="wicri:Area/Pmc/Corpus">002E18</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002E18</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes</title><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="A1">Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.</nlm:aff></affiliation></author><author><name sortKey="Voight, Benjamin F" sort="Voight, Benjamin F" uniqKey="Voight B" first="Benjamin F" last="Voight">Benjamin F. Voight</name><affiliation><nlm:aff id="A2">Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A3">University of Pennsylvania - Perelman School of Medicine, Department of Pharmacology, Philadelphia, Pennsylvania, USA.</nlm:aff></affiliation></author><author><name sortKey="Teslovich, Tanya M" sort="Teslovich, Tanya M" uniqKey="Teslovich T" first="Tanya M" last="Teslovich">Tanya M. Teslovich</name><affiliation><nlm:aff id="A4">Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA.</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="A1">Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.</nlm:aff></affiliation></author><author><name sortKey="Segre, Ayellet V" sort="Segre, Ayellet V" uniqKey="Segre A" first="Ayellet V" last="Segrè">Ayellet V. Segrè</name><affiliation><nlm:aff id="A2">Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A5">Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A6">Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Steinthorsdottir, Valgerdur" sort="Steinthorsdottir, Valgerdur" uniqKey="Steinthorsdottir V" first="Valgerdur" last="Steinthorsdottir">Valgerdur Steinthorsdottir</name><affiliation><nlm:aff id="A7">deCODE Genetics, Reykjavik, Iceland.</nlm:aff></affiliation></author><author><name sortKey="Strawbridge, Rona J" sort="Strawbridge, Rona J" uniqKey="Strawbridge R" first="Rona J" last="Strawbridge">Rona J. Strawbridge</name><affiliation><nlm:aff id="A8">Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.</nlm:aff></affiliation><affiliation><nlm:aff id="A9">Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden.</nlm:aff></affiliation></author><author><name sortKey="Khan, Hassan" sort="Khan, Hassan" uniqKey="Khan H" first="Hassan" last="Khan">Hassan Khan</name><affiliation><nlm:aff id="A10">Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.</nlm:aff></affiliation></author><author><name sortKey="Grallert, Harald" sort="Grallert, Harald" uniqKey="Grallert H" first="Harald" last="Grallert">Harald Grallert</name><affiliation><nlm:aff id="A11">Research Unit of Molecular Epidemiology, Helmholtz Zentrum Muenchen, Neuherberg, Germany.</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="A1">Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.</nlm:aff></affiliation></author><author><name sortKey="Prokopenko, Inga" sort="Prokopenko, Inga" uniqKey="Prokopenko I" first="Inga" last="Prokopenko">Inga Prokopenko</name><affiliation><nlm:aff id="A1">Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.</nlm:aff></affiliation><affiliation><nlm:aff id="A12">Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.</nlm:aff></affiliation></author><author><name sortKey="Kang, Hyun Min" sort="Kang, Hyun Min" uniqKey="Kang H" first="Hyun Min" last="Kang">Hyun Min Kang</name><affiliation><nlm:aff id="A4">Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA.</nlm:aff></affiliation></author><author><name sortKey="Dina, Christian" sort="Dina, Christian" uniqKey="Dina C" first="Christian" last="Dina">Christian Dina</name><affiliation><nlm:aff id="A13">Inserm UMR 1087, Nantes, France.</nlm:aff></affiliation><affiliation><nlm:aff id="A14">CNRS UMR 6291, Nantes, France.</nlm:aff></affiliation><affiliation><nlm:aff id="A15">Nantes University, Nantes, France.</nlm:aff></affiliation></author><author><name sortKey="Esko, Tonu" sort="Esko, Tonu" uniqKey="Esko T" first="Tonu" last="Esko">Tonu Esko</name><affiliation><nlm:aff id="A16">Estonian Genome Center, University of Tartu, Tartu, Estonia.</nlm:aff></affiliation><affiliation><nlm:aff id="A17">Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.</nlm:aff></affiliation></author><author><name sortKey="Fraser, Ross M" sort="Fraser, Ross M" uniqKey="Fraser R" first="Ross M" last="Fraser">Ross M. Fraser</name><affiliation><nlm:aff id="A18">Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK.</nlm:aff></affiliation></author><author><name sortKey="Kanoni, Stavroula" sort="Kanoni, Stavroula" uniqKey="Kanoni S" first="Stavroula" last="Kanoni">Stavroula Kanoni</name><affiliation><nlm:aff id="A19">Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.</nlm:aff></affiliation></author><author><name sortKey="Kumar, Ashish" sort="Kumar, Ashish" uniqKey="Kumar A" first="Ashish" last="Kumar">Ashish Kumar</name><affiliation><nlm:aff id="A1">Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.</nlm:aff></affiliation></author><author><name sortKey="Lagou, Vasiliki" sort="Lagou, Vasiliki" uniqKey="Lagou V" first="Vasiliki" last="Lagou">Vasiliki Lagou</name><affiliation><nlm:aff id="A1">Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, 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="A20">MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.</nlm:aff></affiliation></author><author><name sortKey="Luan, Jian An" sort="Luan, Jian An" uniqKey="Luan J" first="Jian'An" last="Luan">Jian'An Luan</name><affiliation><nlm:aff id="A20">MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, 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="A1">Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.</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="A21">Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany.</nlm:aff></affiliation><affiliation><nlm:aff id="A22">Institute of Genetic Epidemiology, Helmholtz Zentrum Muenchen, Neuherberg, Germany.</nlm:aff></affiliation><affiliation><nlm:aff id="A23">Department of Medicine I, University Hospital Grosshadern, Ludwig-Maximilians-University, Munich, Germany.</nlm:aff></affiliation></author><author><name sortKey="Pechlivanis, Sonali" sort="Pechlivanis, Sonali" uniqKey="Pechlivanis S" first="Sonali" last="Pechlivanis">Sonali Pechlivanis</name><affiliation><nlm:aff id="A24">Institute for Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, University Duisburg-Essen, Essen, Germany.</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="A1">Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.</nlm:aff></affiliation><affiliation><nlm:aff id="A12">Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.</nlm:aff></affiliation></author><author><name sortKey="Scott, Laura J" sort="Scott, Laura J" uniqKey="Scott L" first="Laura J" last="Scott">Laura J. Scott</name><affiliation><nlm:aff id="A4">Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA.</nlm:aff></affiliation></author><author><name sortKey="Wiltshire, Steven" sort="Wiltshire, Steven" uniqKey="Wiltshire S" first="Steven" last="Wiltshire">Steven Wiltshire</name><affiliation><nlm:aff id="A1">Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.</nlm:aff></affiliation></author><author><name sortKey="Yengo, Loic" sort="Yengo, Loic" uniqKey="Yengo L" first="Loic" last="Yengo">Loic Yengo</name><affiliation><nlm:aff id="A25">CNRS-UMR-8199, Institute of Biology and Lille 2 University, Pasteur Institute, Lille, France.</nlm:aff></affiliation><affiliation><nlm:aff id="A26">University Lille 1, Laboratory of Mathematics, CNRS-UMR 8524, MODAL team, INRIA Lille Nord-Europe, Lille, France.</nlm:aff></affiliation></author><author><name sortKey="Kinnunen, Leena" sort="Kinnunen, Leena" uniqKey="Kinnunen L" first="Leena" last="Kinnunen">Leena Kinnunen</name><affiliation><nlm:aff id="A27">Diabetes Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland.</nlm:aff></affiliation></author><author><name sortKey="Rossin, Elizabeth J" sort="Rossin, Elizabeth J" uniqKey="Rossin E" first="Elizabeth J" last="Rossin">Elizabeth J. Rossin</name><affiliation><nlm:aff id="A2">Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A5">Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A28">Health Science and Technology MD Program, Harvard University and Massachusetts Institute of Technology, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A29">Harvard Biological and Biomedical Sciences Program, Harvard University, Boston, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Raychaudhuri, Soumya" sort="Raychaudhuri, Soumya" uniqKey="Raychaudhuri S" first="Soumya" last="Raychaudhuri">Soumya Raychaudhuri</name><affiliation><nlm:aff id="A2">Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A30">Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A31">Partners Center for Personalized Genomic Medicine, Boston, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Johnson, Andrew D" sort="Johnson, Andrew D" uniqKey="Johnson A" first="Andrew D" last="Johnson">Andrew D. Johnson</name><affiliation><nlm:aff id="A32">National Heart, Lung, and Blood Institute’s Framingham Heart Study, Framingham, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Dimas, Antigone S" sort="Dimas, Antigone S" uniqKey="Dimas A" first="Antigone S" last="Dimas">Antigone S. Dimas</name><affiliation><nlm:aff id="A1">Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.</nlm:aff></affiliation><affiliation><nlm:aff id="A33">Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.</nlm:aff></affiliation><affiliation><nlm:aff id="A34">Biomedical Sciences Research Center Al. Fleming, Vari, Greece.</nlm:aff></affiliation></author><author><name sortKey="Loos, Ruth J F" sort="Loos, Ruth J F" uniqKey="Loos R" first="Ruth J F" last="Loos">Ruth J F. Loos</name><affiliation><nlm:aff id="A20">MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.</nlm:aff></affiliation><affiliation><nlm:aff id="A35">Charles R. Bronfman Institute for Personalized Medicine, Mount Sinai School of Medicine, New York, New York, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A36">Child Health and Development Institute, Mount Sinai School of Medicine, New York, New York, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A37">Department of Preventive Medicine, Mount Sinai School of Medicine, New York, New York, USA.</nlm:aff></affiliation></author><author><name sortKey="Vedantam, Sailaja" sort="Vedantam, Sailaja" uniqKey="Vedantam S" first="Sailaja" last="Vedantam">Sailaja Vedantam</name><affiliation><nlm:aff id="A38">Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A39">Division of Genetics and Endocrinology, Children's Hospital, Boston, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Chen, Han" sort="Chen, Han" uniqKey="Chen H" first="Han" last="Chen">Han Chen</name><affiliation><nlm:aff id="A40">Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Florez, Jose C" sort="Florez, Jose C" uniqKey="Florez J" first="Jose C" last="Florez">Jose C. Florez</name><affiliation><nlm:aff id="A5">Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A6">Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A38">Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A41">Diabetes Research Center, Diabetes Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Fox, Caroline" sort="Fox, Caroline" uniqKey="Fox C" first="Caroline" last="Fox">Caroline Fox</name><affiliation><nlm:aff id="A32">National Heart, Lung, and Blood Institute’s Framingham Heart Study, Framingham, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A42">Division of Endocrinology and Metabolism, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Liu, Ching Ti" sort="Liu, Ching Ti" uniqKey="Liu C" first="Ching-Ti" last="Liu">Ching-Ti Liu</name><affiliation><nlm:aff id="A40">Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Rybin, Denis" sort="Rybin, Denis" uniqKey="Rybin D" first="Denis" last="Rybin">Denis Rybin</name><affiliation><nlm:aff id="A43">Boston University Data Coordinating Center, Boston, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Couper, David J" sort="Couper, David J" uniqKey="Couper D" first="David J" last="Couper">David J. Couper</name><affiliation><nlm:aff id="A44">Collaborative Studies Coordinating Center, Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.</nlm:aff></affiliation></author><author><name sortKey="Kao, Wen Hong L" sort="Kao, Wen Hong L" uniqKey="Kao W" first="Wen Hong L" last="Kao">Wen Hong L. Kao</name><affiliation><nlm:aff id="A45">Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.</nlm:aff></affiliation></author><author><name sortKey="Li, Man" sort="Li, Man" uniqKey="Li M" first="Man" last="Li">Man Li</name><affiliation><nlm:aff id="A45">Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.</nlm:aff></affiliation></author><author><name sortKey="Cornelis, Marilyn C" sort="Cornelis, Marilyn C" uniqKey="Cornelis M" first="Marilyn C" last="Cornelis">Marilyn C. Cornelis</name><affiliation><nlm:aff id="A46">Department of Nutrition and Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Kraft, Peter" sort="Kraft, Peter" uniqKey="Kraft P" first="Peter" last="Kraft">Peter Kraft</name><affiliation><nlm:aff id="A46">Department of Nutrition and Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A47">Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Sun, Qi" sort="Sun, Qi" uniqKey="Sun Q" first="Qi" last="Sun">Qi Sun</name><affiliation><nlm:aff id="A46">Department of Nutrition and Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A48">Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Van Dam, Rob M" sort="Van Dam, Rob M" uniqKey="Van Dam R" first="Rob M" last="Van Dam">Rob M. Van Dam</name><affiliation><nlm:aff id="A46">Department of Nutrition and Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A49">Saw Swee Hock School of Public Health, National University of Singapore, Singapore.</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="A4">Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA.</nlm:aff></affiliation></author><author><name sortKey="Chines, Peter S" sort="Chines, Peter S" uniqKey="Chines P" first="Peter S" last="Chines">Peter S. Chines</name><affiliation><nlm:aff id="A50">National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.</nlm:aff></affiliation></author><author><name sortKey="Fischer, Krista" sort="Fischer, Krista" uniqKey="Fischer K" first="Krista" last="Fischer">Krista Fischer</name><affiliation><nlm:aff id="A16">Estonian Genome Center, University of Tartu, Tartu, Estonia.</nlm:aff></affiliation></author><author><name sortKey="Fontanillas, Pierre" sort="Fontanillas, Pierre" uniqKey="Fontanillas P" first="Pierre" last="Fontanillas">Pierre Fontanillas</name><affiliation><nlm:aff id="A2">Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Holmen, Oddgeir L" sort="Holmen, Oddgeir L" uniqKey="Holmen O" first="Oddgeir L" last="Holmen">Oddgeir L. Holmen</name><affiliation><nlm:aff id="A51">HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger, Norway.</nlm:aff></affiliation></author><author><name sortKey="Hunt, Sarah E" sort="Hunt, Sarah E" uniqKey="Hunt S" first="Sarah E" last="Hunt">Sarah E. Hunt</name><affiliation><nlm:aff id="A19">Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.</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="A4">Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA.</nlm:aff></affiliation></author><author><name sortKey="Kong, Augustine" sort="Kong, Augustine" uniqKey="Kong A" first="Augustine" last="Kong">Augustine Kong</name><affiliation><nlm:aff id="A7">deCODE Genetics, Reykjavik, Iceland.</nlm:aff></affiliation></author><author><name sortKey="Lawrence, Robert" sort="Lawrence, Robert" uniqKey="Lawrence R" first="Robert" last="Lawrence">Robert Lawrence</name><affiliation><nlm:aff id="A52">Centre for Genetic Epidemiology and Biostatistics, The University of Western Australia, Nedlands, Australia.</nlm:aff></affiliation></author><author><name sortKey="Meyer, Julia" sort="Meyer, Julia" uniqKey="Meyer J" first="Julia" last="Meyer">Julia Meyer</name><affiliation><nlm:aff id="A22">Institute of Genetic Epidemiology, Helmholtz Zentrum Muenchen, Neuherberg, Germany.</nlm:aff></affiliation></author><author><name sortKey="Perry, John Rb" sort="Perry, John Rb" uniqKey="Perry J" first="John Rb" last="Perry">John Rb Perry</name><affiliation><nlm:aff id="A1">Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.</nlm:aff></affiliation><affiliation><nlm:aff id="A53">Genetics of Complex Traits, Institute of Biomedical and Clinical Science, Peninsula Medical School, University of Exeter, Magdalen Road, Exeter, UK.</nlm:aff></affiliation></author><author><name sortKey="Platou, Carl Gp" sort="Platou, Carl Gp" uniqKey="Platou C" first="Carl Gp" last="Platou">Carl Gp Platou</name><affiliation><nlm:aff id="A51">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="A54">Department of Internal Medicine, Levanger Hospital, Nord-Trøndelag Health Trust, Levanger, Norway.</nlm:aff></affiliation></author><author><name sortKey="Potter, Simon" sort="Potter, Simon" uniqKey="Potter S" first="Simon" last="Potter">Simon Potter</name><affiliation><nlm:aff id="A19">Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.</nlm:aff></affiliation></author><author><name sortKey="Rehnberg, Emil" sort="Rehnberg, Emil" uniqKey="Rehnberg E" first="Emil" last="Rehnberg">Emil Rehnberg</name><affiliation><nlm:aff id="A55">Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.</nlm:aff></affiliation></author><author><name sortKey="Robertson, Neil" sort="Robertson, Neil" uniqKey="Robertson N" first="Neil" last="Robertson">Neil Robertson</name><affiliation><nlm:aff id="A1">Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.</nlm:aff></affiliation><affiliation><nlm:aff id="A12">Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.</nlm:aff></affiliation></author><author><name sortKey="Sivapalaratnam, Suthesh" sort="Sivapalaratnam, Suthesh" uniqKey="Sivapalaratnam S" first="Suthesh" last="Sivapalaratnam">Suthesh Sivapalaratnam</name><affiliation><nlm:aff id="A56">Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.</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="A57">Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.</nlm:aff></affiliation></author><author><name sortKey="Stirrups, Kathleen" sort="Stirrups, Kathleen" uniqKey="Stirrups K" first="Kathleen" last="Stirrups">Kathleen Stirrups</name><affiliation><nlm:aff id="A19">Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.</nlm:aff></affiliation></author><author><name sortKey="Thorleifsson, Gudmar" sort="Thorleifsson, Gudmar" uniqKey="Thorleifsson G" first="Gudmar" last="Thorleifsson">Gudmar Thorleifsson</name><affiliation><nlm:aff id="A7">deCODE Genetics, Reykjavik, Iceland.</nlm:aff></affiliation></author><author><name sortKey="Tikkanen, Emmi" sort="Tikkanen, Emmi" uniqKey="Tikkanen E" first="Emmi" last="Tikkanen">Emmi Tikkanen</name><affiliation><nlm:aff id="A58">Institute for Molecular Medicine Finland (FIMM), Helsinki, Finland.</nlm:aff></affiliation><affiliation><nlm:aff id="A59">Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.</nlm:aff></affiliation></author><author><name sortKey="Wood, Andrew R" sort="Wood, Andrew R" uniqKey="Wood A" first="Andrew R" last="Wood">Andrew R. Wood</name><affiliation><nlm:aff id="A53">Genetics of Complex Traits, Institute of Biomedical and Clinical Science, Peninsula Medical School, University of Exeter, Magdalen Road, Exeter, UK.</nlm:aff></affiliation></author><author><name sortKey="Almgren, Peter" sort="Almgren, Peter" uniqKey="Almgren P" first="Peter" last="Almgren">Peter Almgren</name><affiliation><nlm:aff id="A60">Lund University Diabetes Centre, Department of Clinical Science Malmö, Scania University Hospital, Lund University, Malmö, Sweden.</nlm:aff></affiliation></author><author><name sortKey="Atalay, Mustafa" sort="Atalay, Mustafa" uniqKey="Atalay M" first="Mustafa" last="Atalay">Mustafa Atalay</name><affiliation><nlm:aff id="A61">Institute of Biomedicine, Physiology, University of Eastern Finland, Kuopio Campus, Kuopio, Finland.</nlm:aff></affiliation></author><author><name sortKey="Benediktsson, Rafn" sort="Benediktsson, Rafn" uniqKey="Benediktsson R" first="Rafn" last="Benediktsson">Rafn Benediktsson</name><affiliation><nlm:aff id="A62">Faculty of Medicine, University of Iceland, Reykjavík, Iceland.</nlm:aff></affiliation><affiliation><nlm:aff id="A63">Landspitali University Hospital, Reykjavík, Iceland.</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="A50">National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.</nlm:aff></affiliation></author><author><name sortKey="Burtt, Noel" sort="Burtt, Noel" uniqKey="Burtt N" first="Noël" last="Burtt">Noël Burtt</name><affiliation><nlm:aff id="A2">Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Carey, Jason" sort="Carey, Jason" uniqKey="Carey J" first="Jason" last="Carey">Jason Carey</name><affiliation><nlm:aff id="A2">Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Charpentier, Guillaume" sort="Charpentier, Guillaume" uniqKey="Charpentier G" first="Guillaume" last="Charpentier">Guillaume Charpentier</name><affiliation><nlm:aff id="A64">Endocrinology-Diabetology Unit, Corbeil-Essonnes Hospital, Corbeil-Essonnes, France.</nlm:aff></affiliation></author><author><name sortKey="Crenshaw, Andrew T" sort="Crenshaw, Andrew T" uniqKey="Crenshaw A" first="Andrew T" last="Crenshaw">Andrew T. Crenshaw</name><affiliation><nlm:aff id="A2">Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Doney, Alex S F" sort="Doney, Alex S F" uniqKey="Doney A" first="Alex S F" last="Doney">Alex S F. Doney</name><affiliation><nlm:aff id="A65">Diabetes Research Centre, Biomedical Research Institute, University of Dundee, Ninewells Hospital, Dundee, UK.</nlm:aff></affiliation><affiliation><nlm:aff id="A66">Pharmacogenomics Centre, Biomedical Research Institute, University of Dundee, Ninewells Hospital, Dundee, UK.</nlm:aff></affiliation></author><author><name sortKey="Dorkhan, Mozhgan" sort="Dorkhan, Mozhgan" uniqKey="Dorkhan M" first="Mozhgan" last="Dorkhan">Mozhgan Dorkhan</name><affiliation><nlm:aff id="A60">Lund University Diabetes Centre, Department of Clinical Science Malmö, Scania University Hospital, Lund University, Malmö, Sweden.</nlm:aff></affiliation></author><author><name sortKey="Edkins, Sarah" sort="Edkins, Sarah" uniqKey="Edkins S" first="Sarah" last="Edkins">Sarah Edkins</name><affiliation><nlm:aff id="A19">Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.</nlm:aff></affiliation></author><author><name sortKey="Emilsson, Valur" sort="Emilsson, Valur" uniqKey="Emilsson V" first="Valur" last="Emilsson">Valur Emilsson</name><affiliation><nlm:aff id="A67">Icelandic Heart Association, Kopavogur, Iceland.</nlm:aff></affiliation></author><author><name sortKey="Eury, Elodie" sort="Eury, Elodie" uniqKey="Eury E" first="Elodie" last="Eury">Elodie Eury</name><affiliation><nlm:aff id="A25">CNRS-UMR-8199, Institute of Biology and Lille 2 University, Pasteur Institute, Lille, France.</nlm:aff></affiliation></author><author><name sortKey="Forsen, Tom" sort="Forsen, Tom" uniqKey="Forsen T" first="Tom" last="Forsen">Tom Forsen</name><affiliation><nlm:aff id="A68">Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland.</nlm:aff></affiliation><affiliation><nlm:aff id="A69">Vaasa Health Care Centre, Vaasa, Finland.</nlm:aff></affiliation></author><author><name sortKey="Gertow, Karl" sort="Gertow, Karl" uniqKey="Gertow K" first="Karl" last="Gertow">Karl Gertow</name><affiliation><nlm:aff id="A8">Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.</nlm:aff></affiliation><affiliation><nlm:aff id="A9">Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden.</nlm:aff></affiliation></author><author><name sortKey="Gigante, Bruna" sort="Gigante, Bruna" uniqKey="Gigante B" first="Bruna" last="Gigante">Bruna Gigante</name><affiliation><nlm:aff id="A70">Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.</nlm:aff></affiliation></author><author><name sortKey="Grant, George B" sort="Grant, George B" uniqKey="Grant G" first="George B" last="Grant">George B. Grant</name><affiliation><nlm:aff id="A2">Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, USA.</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="A12">Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.</nlm:aff></affiliation></author><author><name sortKey="Guiducci, Candace" sort="Guiducci, Candace" uniqKey="Guiducci C" first="Candace" last="Guiducci">Candace Guiducci</name><affiliation><nlm:aff id="A2">Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Herder, Christian" sort="Herder, Christian" uniqKey="Herder C" first="Christian" last="Herder">Christian Herder</name><affiliation><nlm:aff id="A71">Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.</nlm:aff></affiliation></author><author><name sortKey="Hreidarsson, Astradur B" sort="Hreidarsson, Astradur B" uniqKey="Hreidarsson A" first="Astradur B" last="Hreidarsson">Astradur B. Hreidarsson</name><affiliation><nlm:aff id="A63">Landspitali University Hospital, Reykjavík, Iceland.</nlm:aff></affiliation></author><author><name sortKey="Hui, Jennie" sort="Hui, Jennie" uniqKey="Hui J" first="Jennie" last="Hui">Jennie Hui</name><affiliation><nlm:aff id="A72">Busselton Population Medical Research Institute, Sir Charles Gairdner Hospital, Nedlands, Australia.</nlm:aff></affiliation><affiliation><nlm:aff id="A73">PathWest Laboratory Medicine of Western Australia, QEII Medical Centre, Nedlands, Australia.</nlm:aff></affiliation><affiliation><nlm:aff id="A74">School of Pathology and Laboratory Medicine, The University of Western Australia, Nedlands, Australia.</nlm:aff></affiliation><affiliation><nlm:aff id="A75">School of Population Health, The University of Western Australia, Nedlands, Australia.</nlm:aff></affiliation></author><author><name sortKey="James, Alan" sort="James, Alan" uniqKey="James A" first="Alan" last="James">Alan James</name><affiliation><nlm:aff id="A72">Busselton Population Medical Research Institute, Sir Charles Gairdner Hospital, Nedlands, Australia.</nlm:aff></affiliation><affiliation><nlm:aff id="A76">Department of Pulmonary Physiology and Sleep Medicine, West Australian Sleep Disorders Research Institute, Queen Elizabeth II Medical Centre, Hospital Avenue, Nedlands, Australia.</nlm:aff></affiliation><affiliation><nlm:aff id="A77">School of Medicine and Pharmacology, University of Western Australia, Nedlands, Australia.</nlm:aff></affiliation></author><author><name sortKey="Jonsson, Anna" sort="Jonsson, Anna" uniqKey="Jonsson A" first="Anna" last="Jonsson">Anna Jonsson</name><affiliation><nlm:aff id="A60">Lund University Diabetes Centre, Department of Clinical Science Malmö, Scania University Hospital, Lund University, Malmö, Sweden.</nlm:aff></affiliation></author><author><name sortKey="Rathmann, Wolfgang" sort="Rathmann, Wolfgang" uniqKey="Rathmann W" first="Wolfgang" last="Rathmann">Wolfgang Rathmann</name><affiliation><nlm:aff id="A78">Institute of Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.</nlm:aff></affiliation></author><author><name sortKey="Klopp, Norman" sort="Klopp, Norman" uniqKey="Klopp N" first="Norman" last="Klopp">Norman Klopp</name><affiliation><nlm:aff id="A11">Research Unit of Molecular Epidemiology, Helmholtz Zentrum Muenchen, Neuherberg, Germany.</nlm:aff></affiliation></author><author><name sortKey="Kravic, Jasmina" sort="Kravic, Jasmina" uniqKey="Kravic J" first="Jasmina" last="Kravic">Jasmina Kravic</name><affiliation><nlm:aff id="A60">Lund University Diabetes Centre, Department of Clinical Science Malmö, Scania University Hospital, Lund University, Malmö, Sweden.</nlm:aff></affiliation></author><author><name sortKey="Krjutskov, Kaarel" sort="Krjutskov, Kaarel" uniqKey="Krjutskov K" first="Kaarel" last="Krjutškov">Kaarel Krjutškov</name><affiliation><nlm:aff id="A16">Estonian Genome Center, University of Tartu, Tartu, Estonia.</nlm:aff></affiliation></author><author><name sortKey="Langford, Cordelia" sort="Langford, Cordelia" uniqKey="Langford C" first="Cordelia" last="Langford">Cordelia Langford</name><affiliation><nlm:aff id="A19">Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.</nlm:aff></affiliation></author><author><name sortKey="Leander, Karin" sort="Leander, Karin" uniqKey="Leander K" first="Karin" last="Leander">Karin Leander</name><affiliation><nlm:aff id="A70">Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.</nlm:aff></affiliation></author><author><name sortKey="Lindholm, Eero" sort="Lindholm, Eero" uniqKey="Lindholm E" first="Eero" last="Lindholm">Eero Lindholm</name><affiliation><nlm:aff id="A60">Lund University Diabetes Centre, Department of Clinical Science Malmö, Scania University Hospital, Lund University, Malmö, Sweden.</nlm:aff></affiliation></author><author><name sortKey="Lobbens, Stephane" sort="Lobbens, Stephane" uniqKey="Lobbens S" first="Stéphane" last="Lobbens">Stéphane Lobbens</name><affiliation><nlm:aff id="A25">CNRS-UMR-8199, Institute of Biology and Lille 2 University, Pasteur Institute, Lille, France.</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="A59">Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.</nlm:aff></affiliation></author><author><name sortKey="Mirza, Ghazala" sort="Mirza, Ghazala" uniqKey="Mirza G" first="Ghazala" last="Mirza">Ghazala Mirza</name><affiliation><nlm:aff id="A1">Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.</nlm:aff></affiliation></author><author><name sortKey="Muhleisen, Thomas W" sort="Muhleisen, Thomas W" uniqKey="Muhleisen T" first="Thomas W" last="Mühleisen">Thomas W. Mühleisen</name><affiliation><nlm:aff id="A79">Institute of Human Genetics, University of Bonn, Bonn, Germany.</nlm:aff></affiliation><affiliation><nlm:aff id="A80">Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.</nlm:aff></affiliation></author><author><name sortKey="Musk, Bill" sort="Musk, Bill" uniqKey="Musk B" first="Bill" last="Musk">Bill Musk</name><affiliation><nlm:aff id="A72">Busselton Population Medical Research Institute, Sir Charles Gairdner Hospital, Nedlands, Australia.</nlm:aff></affiliation><affiliation><nlm:aff id="A75">School of Population Health, The University of Western Australia, Nedlands, Australia.</nlm:aff></affiliation><affiliation><nlm:aff id="A77">School of Medicine and Pharmacology, University of Western Australia, Nedlands, Australia.</nlm:aff></affiliation><affiliation><nlm:aff id="A81">Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, Australia.</nlm:aff></affiliation></author><author><name sortKey="Parkin, Melissa" sort="Parkin, Melissa" uniqKey="Parkin M" first="Melissa" last="Parkin">Melissa Parkin</name><affiliation><nlm:aff id="A2">Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Rallidis, Loukianos" sort="Rallidis, Loukianos" uniqKey="Rallidis L" first="Loukianos" last="Rallidis">Loukianos Rallidis</name><affiliation><nlm:aff id="A82">University General Hospital Attikon, Athens, Greece.</nlm:aff></affiliation></author><author><name sortKey="Saramies, Jouko" sort="Saramies, Jouko" uniqKey="Saramies J" first="Jouko" last="Saramies">Jouko Saramies</name><affiliation><nlm:aff id="A83">South Karelia Central Hospital, Lappeenranta, Finland.</nlm:aff></affiliation></author><author><name sortKey="Sennblad, Bengt" sort="Sennblad, Bengt" uniqKey="Sennblad B" first="Bengt" last="Sennblad">Bengt Sennblad</name><affiliation><nlm:aff id="A8">Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.</nlm:aff></affiliation><affiliation><nlm:aff id="A9">Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden.</nlm:aff></affiliation></author><author><name sortKey="Shah, Sonia" sort="Shah, Sonia" uniqKey="Shah S" first="Sonia" last="Shah">Sonia Shah</name><affiliation><nlm:aff id="A84">UCL Genetics Institute, Department of Genetics, Evolution and Environment, University College London, London, UK.</nlm:aff></affiliation></author><author><name sortKey="Sigur Sson, Gunnar" sort="Sigur Sson, Gunnar" uniqKey="Sigur Sson G" first="Gunnar" last="Sigur Sson">Gunnar Sigur Sson</name><affiliation><nlm:aff id="A63">Landspitali University Hospital, Reykjavík, Iceland.</nlm:aff></affiliation><affiliation><nlm:aff id="A67">Icelandic Heart Association, Kopavogur, Iceland.</nlm:aff></affiliation></author><author><name sortKey="Silveira, Angela" sort="Silveira, Angela" uniqKey="Silveira A" first="Angela" last="Silveira">Angela Silveira</name><affiliation><nlm:aff id="A8">Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.</nlm:aff></affiliation><affiliation><nlm:aff id="A9">Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden.</nlm:aff></affiliation></author><author><name sortKey="Steinbach, Gerald" sort="Steinbach, Gerald" uniqKey="Steinbach G" first="Gerald" last="Steinbach">Gerald Steinbach</name><affiliation><nlm:aff id="A85">Department of Clinical Chemistry and Central Laboratory, University of Ulm, Ulm, Germany.</nlm:aff></affiliation></author><author><name sortKey="Thorand, Barbara" sort="Thorand, Barbara" uniqKey="Thorand B" first="Barbara" last="Thorand">Barbara Thorand</name><affiliation><nlm:aff id="A86">Institute of Epidemiology II, Helmholtz Zentrum Muenchen, Neuherberg, Germany.</nlm:aff></affiliation></author><author><name sortKey="Trakalo, Joseph" sort="Trakalo, Joseph" uniqKey="Trakalo J" first="Joseph" last="Trakalo">Joseph Trakalo</name><affiliation><nlm:aff id="A1">Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.</nlm:aff></affiliation></author><author><name sortKey="Veglia, Fabrizio" sort="Veglia, Fabrizio" uniqKey="Veglia F" first="Fabrizio" last="Veglia">Fabrizio Veglia</name><affiliation><nlm:aff id="A87">Centro Cardiologico Monzino, IRCCS, Milan, Italy.</nlm:aff></affiliation></author><author><name sortKey="Wennauer, Roman" sort="Wennauer, Roman" uniqKey="Wennauer R" first="Roman" last="Wennauer">Roman Wennauer</name><affiliation><nlm:aff id="A85">Department of Clinical Chemistry and Central Laboratory, University of Ulm, Ulm, Germany.</nlm:aff></affiliation></author><author><name sortKey="Winckler, Wendy" sort="Winckler, Wendy" uniqKey="Winckler W" first="Wendy" last="Winckler">Wendy Winckler</name><affiliation><nlm:aff id="A2">Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Zabaneh, Delilah" sort="Zabaneh, Delilah" uniqKey="Zabaneh D" first="Delilah" last="Zabaneh">Delilah Zabaneh</name><affiliation><nlm:aff id="A84">UCL Genetics Institute, Department of Genetics, Evolution and Environment, University College London, London, UK.</nlm:aff></affiliation></author><author><name sortKey="Campbell, Harry" sort="Campbell, Harry" uniqKey="Campbell H" first="Harry" last="Campbell">Harry Campbell</name><affiliation><nlm:aff id="A18">Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK.</nlm:aff></affiliation><affiliation><nlm:aff id="A88">MRC Institute of Genetics and Molecular Medicine at the University of Edinburgh, Western General Hospital, Edinburgh, UK.</nlm:aff></affiliation></author><author><name sortKey="Van Duijn, Cornelia" sort="Van Duijn, Cornelia" uniqKey="Van Duijn C" first="Cornelia" last="Van Duijn">Cornelia Van Duijn</name><affiliation><nlm:aff id="A89">Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.</nlm:aff></affiliation><affiliation><nlm:aff id="A90">Netherland Genomics Initiative, Netherlands Consortium for Healthy Ageing and Centre for Medical Systems Biology, Rotterdam, The Netherlands.</nlm:aff></affiliation></author><author><name sortKey="Uitterlinden89, Andre G" sort="Uitterlinden89, Andre G" uniqKey="Uitterlinden89 A" first="Andre G" last="Uitterlinden89-">Andre G. Uitterlinden89-</name><affiliation><nlm:aff id="A89">Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.</nlm:aff></affiliation><affiliation><nlm:aff id="A90">Netherland Genomics Initiative, Netherlands Consortium for Healthy Ageing and Centre for Medical Systems Biology, Rotterdam, The Netherlands.</nlm:aff></affiliation><affiliation><nlm:aff id="A91">Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.</nlm:aff></affiliation></author><author><name sortKey="Hofman, Albert" sort="Hofman, Albert" uniqKey="Hofman A" first="Albert" last="Hofman">Albert Hofman</name><affiliation><nlm:aff id="A89">Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.</nlm:aff></affiliation></author><author><name sortKey="Sijbrands, Eric" sort="Sijbrands, Eric" uniqKey="Sijbrands E" first="Eric" last="Sijbrands">Eric Sijbrands</name><affiliation><nlm:aff id="A91">Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.</nlm:aff></affiliation></author><author><name sortKey="Abecasis, Goncalo R" sort="Abecasis, Goncalo R" uniqKey="Abecasis G" first="Goncalo R" last="Abecasis">Goncalo R. Abecasis</name><affiliation><nlm:aff id="A4">Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA.</nlm:aff></affiliation></author><author><name sortKey="Owen, Katharine R" sort="Owen, Katharine R" uniqKey="Owen K" first="Katharine R" last="Owen">Katharine R. Owen</name><affiliation><nlm:aff id="A12">Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.</nlm:aff></affiliation><affiliation><nlm:aff id="A92">Oxford National Institute for Health Research Biomedical Research Centre, Churchill Hospital, Oxford, 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="A19">Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.</nlm:aff></affiliation></author><author><name sortKey="Trip, Mieke D" sort="Trip, Mieke D" uniqKey="Trip M" first="Mieke D" last="Trip">Mieke D. Trip</name><affiliation><nlm:aff id="A56">Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.</nlm:aff></affiliation></author><author><name sortKey="Forouhi, Nita G" sort="Forouhi, Nita G" uniqKey="Forouhi N" first="Nita G" last="Forouhi">Nita G. Forouhi</name><affiliation><nlm:aff id="A20">MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.</nlm:aff></affiliation></author><author><name sortKey="Syv Nen, Ann Christine" sort="Syv Nen, Ann Christine" uniqKey="Syv Nen A" first="Ann-Christine" last="Syv Nen">Ann-Christine Syv Nen</name><affiliation><nlm:aff id="A93">Molecular Medicine, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.</nlm:aff></affiliation></author><author><name sortKey="Eriksson, Johan G" sort="Eriksson, Johan G" uniqKey="Eriksson J" first="Johan G" last="Eriksson">Johan G. Eriksson</name><affiliation><nlm:aff id="A59">Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.</nlm:aff></affiliation><affiliation><nlm:aff id="A68">Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland.</nlm:aff></affiliation><affiliation><nlm:aff id="A94">Unit of General Practice, Helsinki University General Hospital, Helsinki, Finland.</nlm:aff></affiliation><affiliation><nlm:aff id="A95">Folkhälsan Research Center, Helsinki, Finland.</nlm:aff></affiliation></author><author><name sortKey="Peltonen, Leena" sort="Peltonen, Leena" uniqKey="Peltonen L" first="Leena" last="Peltonen">Leena Peltonen</name><affiliation><nlm:aff id="A2">Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A19">Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.</nlm:aff></affiliation><affiliation><nlm:aff id="A58">Institute for Molecular Medicine Finland (FIMM), Helsinki, Finland.</nlm:aff></affiliation><affiliation><nlm:aff id="A59">Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.</nlm:aff></affiliation></author><author><name sortKey="Nothen, Markus M" sort="Nothen, Markus M" uniqKey="Nothen M" first="Markus M" last="Nöthen">Markus M. Nöthen</name><affiliation><nlm:aff id="A79">Institute of Human Genetics, University of Bonn, Bonn, Germany.</nlm:aff></affiliation><affiliation><nlm:aff id="A80">Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.</nlm:aff></affiliation></author><author><name sortKey="Balkau, Beverley" sort="Balkau, Beverley" uniqKey="Balkau B" first="Beverley" last="Balkau">Beverley Balkau</name><affiliation><nlm:aff id="A96">INSERM CESP U1018, Villejuif, France.</nlm:aff></affiliation><affiliation><nlm:aff id="A97">University Paris Sud 11, UMRS 1018, Villejuif, France.</nlm:aff></affiliation></author><author><name sortKey="Palmer, Colin N A" sort="Palmer, Colin N A" uniqKey="Palmer C" first="Colin N A" last="Palmer">Colin N A. Palmer</name><affiliation><nlm:aff id="A65">Diabetes Research Centre, Biomedical Research Institute, University of Dundee, Ninewells Hospital, Dundee, UK.</nlm:aff></affiliation><affiliation><nlm:aff id="A66">Pharmacogenomics Centre, Biomedical Research Institute, University of Dundee, Ninewells Hospital, Dundee, UK.</nlm:aff></affiliation></author><author><name sortKey="Lyssenko, Valeriya" sort="Lyssenko, Valeriya" uniqKey="Lyssenko V" first="Valeriya" last="Lyssenko">Valeriya Lyssenko</name><affiliation><nlm:aff id="A60">Lund University Diabetes Centre, Department of Clinical Science Malmö, Scania University Hospital, Lund University, Malmö, Sweden.</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="A95">Folkhälsan Research Center, Helsinki, Finland.</nlm:aff></affiliation><affiliation><nlm:aff id="A98">Department of Medicine, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.</nlm:aff></affiliation></author><author><name sortKey="Isomaa, Bo" sort="Isomaa, Bo" uniqKey="Isomaa B" first="Bo" last="Isomaa">Bo Isomaa</name><affiliation><nlm:aff id="A95">Folkhälsan Research Center, Helsinki, Finland.</nlm:aff></affiliation><affiliation><nlm:aff id="A99">Department of Social Services and Health Care, Jakobstad, Finland.</nlm:aff></affiliation></author><author><name sortKey="Hunter, David J" sort="Hunter, David J" uniqKey="Hunter D" first="David J" last="Hunter">David J. Hunter</name><affiliation><nlm:aff id="A46">Department of Nutrition and Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A47">Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A48">Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Qi, Lu" sort="Qi, Lu" uniqKey="Qi L" first="Lu" last="Qi">Lu Qi</name><affiliation><nlm:aff id="A46">Department of Nutrition and Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A48">Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Shuldiner, Alan R" sort="Shuldiner, Alan R" uniqKey="Shuldiner A" first="Alan R" last="Shuldiner">Alan R. Shuldiner</name><affiliation><nlm:aff id="A100">Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A101">Geriatric Research Education and Clinical Center, Baltimore Veterans Administration Medical Center, Baltimore, Maryland, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A102">Program in Personalised and Genomic Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.</nlm:aff></affiliation></author><author><name sortKey="Roden, Michael" sort="Roden, Michael" uniqKey="Roden M" first="Michael" last="Roden">Michael Roden</name><affiliation><nlm:aff id="A71">Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.</nlm:aff></affiliation><affiliation><nlm:aff id="A103">Department of Medicine/Metabolic Diseases, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.</nlm:aff></affiliation></author><author><name sortKey="Barroso, Ines" sort="Barroso, Ines" uniqKey="Barroso I" first="Ines" last="Barroso">Ines Barroso</name><affiliation><nlm:aff id="A19">Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.</nlm:aff></affiliation><affiliation><nlm:aff id="A104">University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge, UK.</nlm:aff></affiliation><affiliation><nlm:aff id="A105">NIHR Cambridge Biomedical Research Centre, Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge, UK.</nlm:aff></affiliation></author><author><name sortKey="Wilsgaard, Tom" sort="Wilsgaard, Tom" uniqKey="Wilsgaard T" first="Tom" last="Wilsgaard">Tom Wilsgaard</name><affiliation><nlm:aff id="A106">Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway.</nlm:aff></affiliation></author><author><name sortKey="Beilby, John" sort="Beilby, John" uniqKey="Beilby J" first="John" last="Beilby">John Beilby</name><affiliation><nlm:aff id="A72">Busselton Population Medical Research Institute, Sir Charles Gairdner Hospital, Nedlands, Australia.</nlm:aff></affiliation><affiliation><nlm:aff id="A73">PathWest Laboratory Medicine of Western Australia, QEII Medical Centre, Nedlands, Australia.</nlm:aff></affiliation><affiliation><nlm:aff id="A74">School of Pathology and Laboratory Medicine, The University of Western Australia, Nedlands, Australia.</nlm:aff></affiliation></author><author><name sortKey="Hovingh, Kees" sort="Hovingh, Kees" uniqKey="Hovingh K" first="Kees" last="Hovingh">Kees Hovingh</name><affiliation><nlm:aff id="A56">Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.</nlm:aff></affiliation></author><author><name sortKey="Price, Jackie F" sort="Price, Jackie F" uniqKey="Price J" first="Jackie F" last="Price">Jackie F. Price</name><affiliation><nlm:aff id="A18">Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK.</nlm:aff></affiliation></author><author><name sortKey="Wilson, James F" sort="Wilson, James F" uniqKey="Wilson J" first="James F" last="Wilson">James F. Wilson</name><affiliation><nlm:aff id="A18">Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK.</nlm:aff></affiliation><affiliation><nlm:aff id="A88">MRC Institute of Genetics and Molecular Medicine at the University of Edinburgh, Western General Hospital, Edinburgh, UK.</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="A107">Kuopio Research Institute of Exercise Medicine, Kuopio, Finland.</nlm:aff></affiliation><affiliation><nlm:aff id="A108">Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, 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="A61">Institute of Biomedicine, Physiology, University of Eastern Finland, Kuopio Campus, Kuopio, Finland.</nlm:aff></affiliation><affiliation><nlm:aff id="A107">Kuopio Research Institute of Exercise Medicine, Kuopio, Finland.</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="A109">Department of Medical Sciences, Uppsala University, Akademiska Sjukhuset, Uppsala, Sweden.</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="A110">Department of Dietetics-Nutrition, Harokopio University, Athens, Greece.</nlm:aff></affiliation></author><author><name sortKey="Nj Lstad, Inger" sort="Nj Lstad, Inger" uniqKey="Nj Lstad I" first="Inger" last="Nj Lstad">Inger Nj Lstad</name><affiliation><nlm:aff id="A106">Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway.</nlm:aff></affiliation></author><author><name sortKey="Pedersen, Nancy L" sort="Pedersen, Nancy L" uniqKey="Pedersen N" first="Nancy L" last="Pedersen">Nancy L. Pedersen</name><affiliation><nlm:aff id="A55">Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.</nlm:aff></affiliation></author><author><name sortKey="Khaw, Kay Tee" sort="Khaw, Kay Tee" uniqKey="Khaw K" first="Kay-Tee" last="Khaw">Kay-Tee Khaw</name><affiliation><nlm:aff id="A10">Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.</nlm:aff></affiliation></author><author><name sortKey="Wareham, Nicholas J" sort="Wareham, Nicholas J" uniqKey="Wareham N" first="Nicholas J" last="Wareham">Nicholas J. Wareham</name><affiliation><nlm:aff id="A20">MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.</nlm:aff></affiliation></author><author><name sortKey="Keinanen Kiukaanniemi, Sirkka M" sort="Keinanen Kiukaanniemi, Sirkka M" uniqKey="Keinanen Kiukaanniemi S" first="Sirkka M" last="Keinanen-Kiukaanniemi">Sirkka M. Keinanen-Kiukaanniemi</name><affiliation><nlm:aff id="A111">Faculty of Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland.</nlm:aff></affiliation><affiliation><nlm:aff id="A112">Unit of General Practice, Oulu University Hospital, Oulu, Finland.</nlm:aff></affiliation></author><author><name sortKey="Saaristo, Timo E" sort="Saaristo, Timo E" uniqKey="Saaristo T" first="Timo E" last="Saaristo">Timo E. Saaristo</name><affiliation><nlm:aff id="A113">Finnish Diabetes Association, Tampere, Finland.</nlm:aff></affiliation><affiliation><nlm:aff id="A114">Pirkanmaa Hospital District, Tampere, Finland.</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="A115">South Ostrobothnia Central Hospital, Seinäjoki, Finland.</nlm:aff></affiliation></author><author><name sortKey="Saltevo, Juha" sort="Saltevo, Juha" uniqKey="Saltevo J" first="Juha" last="Saltevo">Juha Saltevo</name><affiliation><nlm:aff id="A116">Department of Medicine, Central Finland Central Hospital, Jyväskylä, 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="A57">Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.</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="A57">Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.</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="A16">Estonian Genome Center, University of Tartu, Tartu, Estonia.</nlm:aff></affiliation><affiliation><nlm:aff id="A17">Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.</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="A50">National Human Genome Research Institute, National Institutes of Health, 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="A117">Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA.</nlm:aff></affiliation></author><author><name sortKey="Bergman, Richard N" sort="Bergman, Richard N" uniqKey="Bergman R" first="Richard N" last="Bergman">Richard N. Bergman</name><affiliation><nlm:aff id="A118">Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.</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="A27">Diabetes Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland.</nlm:aff></affiliation><affiliation><nlm:aff id="A115">South Ostrobothnia Central Hospital, Seinäjoki, Finland.</nlm:aff></affiliation><affiliation><nlm:aff id="A119">Red RECAVA Grupo RD06/0014/0015, Hospital Universitario La Paz, Madrid, Spain.</nlm:aff></affiliation><affiliation><nlm:aff id="A120">Centre for Vascular Prevention, Danube-University Krems, Krems, Austria.</nlm:aff></affiliation></author><author><name sortKey="Boehm, Bernhard O" sort="Boehm, Bernhard O" uniqKey="Boehm B" first="Bernhard O" last="Boehm">Bernhard O. Boehm</name><affiliation><nlm:aff id="A121">Division of Endocrinology and Diabetes, Department of Internal Medicine, University Medical Centre Ulm, Ulm, Germany.</nlm:aff></affiliation></author><author><name sortKey="Gieger, Christian" sort="Gieger, Christian" uniqKey="Gieger C" first="Christian" last="Gieger">Christian Gieger</name><affiliation><nlm:aff id="A22">Institute of Genetic Epidemiology, Helmholtz Zentrum Muenchen, Neuherberg, Germany.</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="A51">HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger, Norway.</nlm:aff></affiliation></author><author><name sortKey="Cauchi, Stephane" sort="Cauchi, Stephane" uniqKey="Cauchi S" first="Stephane" last="Cauchi">Stephane Cauchi</name><affiliation><nlm:aff id="A25">CNRS-UMR-8199, Institute of Biology and Lille 2 University, Pasteur Institute, Lille, France.</nlm:aff></affiliation></author><author><name sortKey="Froguel, Philippe" sort="Froguel, Philippe" uniqKey="Froguel P" first="Philippe" last="Froguel">Philippe Froguel</name><affiliation><nlm:aff id="A25">CNRS-UMR-8199, Institute of Biology and Lille 2 University, Pasteur Institute, Lille, France.</nlm:aff></affiliation><affiliation><nlm:aff id="A122">Genomic Medicine, Imperial College London, Hammersmith Hospital, London, UK.</nlm:aff></affiliation></author><author><name sortKey="Baldassarre, Damiano" sort="Baldassarre, Damiano" uniqKey="Baldassarre D" first="Damiano" last="Baldassarre">Damiano Baldassarre</name><affiliation><nlm:aff id="A87">Centro Cardiologico Monzino, IRCCS, Milan, Italy.</nlm:aff></affiliation><affiliation><nlm:aff id="A123">Department of Pharmacological Sciences, University of Milan, Milan, Italy.</nlm:aff></affiliation></author><author><name sortKey="Tremoli, Elena" sort="Tremoli, Elena" uniqKey="Tremoli E" first="Elena" last="Tremoli">Elena Tremoli</name><affiliation><nlm:aff id="A87">Centro Cardiologico Monzino, IRCCS, Milan, Italy.</nlm:aff></affiliation><affiliation><nlm:aff id="A123">Department of Pharmacological Sciences, University of Milan, Milan, Italy.</nlm:aff></affiliation></author><author><name sortKey="Humphries, Steve E" sort="Humphries, Steve E" uniqKey="Humphries S" first="Steve E" last="Humphries">Steve E. Humphries</name><affiliation><nlm:aff id="A124">Institute of Cardiovascular Science, University College London, London, 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="A10">Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.</nlm:aff></affiliation><affiliation><nlm:aff id="A125">Center for Non-Communicable Diseases Pakistan, Karachi, Pakistan.</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="A10">Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.</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="A55">Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.</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="A19">Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.</nlm:aff></affiliation><affiliation><nlm:aff id="A58">Institute for Molecular Medicine Finland (FIMM), Helsinki, Finland.</nlm:aff></affiliation><affiliation><nlm:aff id="A59">Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.</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="A59">Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.</nlm:aff></affiliation></author><author><name sortKey="Erbel, Raimund" sort="Erbel, Raimund" uniqKey="Erbel R" first="Raimund" last="Erbel">Raimund Erbel</name><affiliation><nlm:aff id="A126">Clinic of Cardiology, West German Heart Centre, University Hospital of Essen, University Duisburg-Essen, Essen, Germany.</nlm:aff></affiliation></author><author><name sortKey="Jockel, Karl Heinz" sort="Jockel, Karl Heinz" uniqKey="Jockel K" first="Karl-Heinz" last="Jöckel">Karl-Heinz Jöckel</name><affiliation><nlm:aff id="A24">Institute for Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, University Duisburg-Essen, Essen, Germany.</nlm:aff></affiliation></author><author><name sortKey="Moebus, Susanne" sort="Moebus, Susanne" uniqKey="Moebus S" first="Susanne" last="Moebus">Susanne Moebus</name><affiliation><nlm:aff id="A24">Institute for Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, University Duisburg-Essen, Essen, Germany.</nlm:aff></affiliation></author><author><name sortKey="Peters, Annette" sort="Peters, Annette" uniqKey="Peters A" first="Annette" last="Peters">Annette Peters</name><affiliation><nlm:aff id="A86">Institute of Epidemiology II, Helmholtz Zentrum Muenchen, Neuherberg, Germany.</nlm:aff></affiliation></author><author><name sortKey="Illig, Thomas" sort="Illig, Thomas" uniqKey="Illig T" first="Thomas" last="Illig">Thomas Illig</name><affiliation><nlm:aff id="A11">Research Unit of Molecular Epidemiology, Helmholtz Zentrum Muenchen, Neuherberg, Germany.</nlm:aff></affiliation><affiliation><nlm:aff id="A127">Hannover Unified Biobank, Hannover Medical School, Hannover, Germany.</nlm:aff></affiliation></author><author><name sortKey="De Faire, Ulf" sort="De Faire, Ulf" uniqKey="De Faire U" first="Ulf" last="De Faire">Ulf De Faire</name><affiliation><nlm:aff id="A70">Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.</nlm:aff></affiliation></author><author><name sortKey="Hamsten, Anders" sort="Hamsten, Anders" uniqKey="Hamsten A" first="Anders" last="Hamsten">Anders Hamsten</name><affiliation><nlm:aff id="A8">Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.</nlm:aff></affiliation><affiliation><nlm:aff id="A9">Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden.</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="A65">Diabetes Research Centre, Biomedical Research Institute, University of Dundee, Ninewells Hospital, Dundee, UK.</nlm:aff></affiliation><affiliation><nlm:aff id="A66">Pharmacogenomics Centre, Biomedical Research Institute, University of Dundee, Ninewells Hospital, Dundee, UK.</nlm:aff></affiliation></author><author><name sortKey="Donnelly, Peter J" sort="Donnelly, Peter J" uniqKey="Donnelly P" first="Peter J" last="Donnelly">Peter J. Donnelly</name><affiliation><nlm:aff id="A1">Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.</nlm:aff></affiliation><affiliation><nlm:aff id="A128">Department of Statistics, University of Oxford, Oxford, UK.</nlm:aff></affiliation></author><author><name sortKey="Frayling, Timothy M" sort="Frayling, Timothy M" uniqKey="Frayling T" first="Timothy M" last="Frayling">Timothy M. Frayling</name><affiliation><nlm:aff id="A53">Genetics of Complex Traits, Institute of Biomedical and Clinical Science, Peninsula Medical School, University of Exeter, Magdalen Road, Exeter, UK.</nlm:aff></affiliation></author><author><name sortKey="Hattersley, Andrew T" sort="Hattersley, Andrew T" uniqKey="Hattersley A" first="Andrew T" last="Hattersley">Andrew T. Hattersley</name><affiliation><nlm:aff id="A129">Diabetes Genetics, Institute of Biomedical and Clinical Science, Peninsula Medical School, University of Exeter, Exeter, UK.</nlm:aff></affiliation></author><author><name sortKey="Boerwinkle, Eric" sort="Boerwinkle, Eric" uniqKey="Boerwinkle E" first="Eric" last="Boerwinkle">Eric Boerwinkle</name><affiliation><nlm:aff id="A130">Human Genetics Center, University of Texas Health Science Center at Houston, Houston, Texas, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A131">Human Genome Sequencing Center at Baylor College of Medicine, Houston, Texas, 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="A60">Lund University Diabetes Centre, Department of Clinical Science Malmö, Scania University Hospital, Lund University, Malmö, Sweden.</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="A2">Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A5">Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A132">Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Nilsson, Peter M" sort="Nilsson, Peter M" uniqKey="Nilsson P" first="Peter M" last="Nilsson">Peter M. Nilsson</name><affiliation><nlm:aff id="A60">Lund University Diabetes Centre, Department of Clinical Science Malmö, Scania University Hospital, Lund University, Malmö, Sweden.</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="A19">Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.</nlm:aff></affiliation></author><author><name sortKey="Thorsteinsdottir, Unnur" sort="Thorsteinsdottir, Unnur" uniqKey="Thorsteinsdottir U" first="Unnur" last="Thorsteinsdottir">Unnur Thorsteinsdottir</name><affiliation><nlm:aff id="A7">deCODE Genetics, Reykjavik, Iceland.</nlm:aff></affiliation><affiliation><nlm:aff id="A62">Faculty of Medicine, University of Iceland, Reykjavík, Iceland.</nlm:aff></affiliation></author><author><name sortKey="Groop, Leif C" sort="Groop, Leif C" uniqKey="Groop L" first="Leif C" last="Groop">Leif C. Groop</name><affiliation><nlm:aff id="A60">Lund University Diabetes Centre, Department of Clinical Science Malmö, Scania University Hospital, Lund University, Malmö, Sweden.</nlm:aff></affiliation></author><author><name sortKey="Stefansson, Kari" sort="Stefansson, Kari" uniqKey="Stefansson K" first="Kari" last="Stefansson">Kari Stefansson</name><affiliation><nlm:aff id="A7">deCODE Genetics, Reykjavik, Iceland.</nlm:aff></affiliation><affiliation><nlm:aff id="A62">Faculty of Medicine, University of Iceland, Reykjavík, Iceland.</nlm:aff></affiliation></author><author><name sortKey="Hu, Frank" sort="Hu, Frank" uniqKey="Hu F" first="Frank" last="Hu">Frank Hu</name><affiliation><nlm:aff id="A46">Department of Nutrition and Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A48">Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Pankow, James S" sort="Pankow, James S" uniqKey="Pankow J" first="James S" last="Pankow">James S. Pankow</name><affiliation><nlm:aff id="A133">Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, Minnesota, USA.</nlm:aff></affiliation></author><author><name sortKey="Dupuis, Josee" sort="Dupuis, Josee" uniqKey="Dupuis J" first="Josée" last="Dupuis">Josée Dupuis</name><affiliation><nlm:aff id="A32">National Heart, Lung, and Blood Institute’s Framingham Heart Study, Framingham, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A40">Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Meigs, James B" sort="Meigs, James B" uniqKey="Meigs J" first="James B" last="Meigs">James B. Meigs</name><affiliation><nlm:aff id="A6">Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A134">General Medicine Division, Massachusetts General Hospital, Boston, Massachusetts, USA.</nlm:aff></affiliation></author><author><name sortKey="Altshuler, David" sort="Altshuler, David" uniqKey="Altshuler D" first="David" last="Altshuler">David Altshuler</name><affiliation><nlm:aff id="A2">Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A5">Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A6">Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A135">Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A136">Department of Molecular Biology, Harvard Medical School, Boston, Massachusetts, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A137">Diabetes Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.</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="A4">Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA.</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="A1">Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.</nlm:aff></affiliation><affiliation><nlm:aff id="A12">Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.</nlm:aff></affiliation><affiliation><nlm:aff id="A92">Oxford National Institute for Health Research Biomedical Research Centre, Churchill Hospital, Oxford, 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="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P5">To extend understanding of the genetic architecture and molecular basis of type 2 diabetes (T2D), we conducted a meta-analysis of genetic variants on the Metabochip involving 34,840 cases and 114,981 controls, overwhelmingly of European descent. We identified ten previously unreported T2D susceptibility loci, including two demonstrating sex-differentiated association. Genome-wide analyses of these data are consistent with a long tail of further common variant loci explaining much of the variation in susceptibility to T2D. Exploration of the enlarged set of susceptibility loci implicates several processes, including CREBBP-related transcription, adipocytokine signalling and cell cycle regulation, in diabetes pathogenesis.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Stumvoll, M" uniqKey="Stumvoll M">M Stumvoll</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zeggini, E" uniqKey="Zeggini E">E Zeggini</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kong, A" uniqKey="Kong A">A Kong</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Voight, Bf" uniqKey="Voight B">BF Voight</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dupuis, J" uniqKey="Dupuis J">J Dupuis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Qi, L" uniqKey="Qi L">L 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<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">22885922</article-id><article-id pub-id-type="pmc">3442244</article-id><article-id pub-id-type="doi">10.1038/ng.2383</article-id><article-id pub-id-type="manuscript">NIHMS393294</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Morris</surname><given-names>Andrew P</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="author-notes" rid="FN3">140</xref></contrib><contrib 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contrib-type="author"><name><surname>Steinthorsdottir</surname><given-names>Valgerdur</given-names></name><xref ref-type="aff" rid="A7">7</xref></contrib><contrib contrib-type="author"><name><surname>Strawbridge</surname><given-names>Rona J</given-names></name><xref ref-type="aff" rid="A8">8</xref><xref ref-type="aff" rid="A9">9</xref></contrib><contrib contrib-type="author"><name><surname>Khan</surname><given-names>Hassan</given-names></name><xref ref-type="aff" rid="A10">10</xref></contrib><contrib contrib-type="author"><name><surname>Grallert</surname><given-names>Harald</given-names></name><xref ref-type="aff" rid="A11">11</xref></contrib><contrib contrib-type="author"><name><surname>Mahajan</surname><given-names>Anubha</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Prokopenko</surname><given-names>Inga</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A12">12</xref></contrib><contrib contrib-type="author"><name><surname>Kang</surname><given-names>Hyun Min</given-names></name><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Dina</surname><given-names>Christian</given-names></name><xref ref-type="aff" rid="A13">13</xref><xref ref-type="aff" rid="A14">14</xref><xref ref-type="aff" rid="A15">15</xref></contrib><contrib contrib-type="author"><name><surname>Esko</surname><given-names>Tonu</given-names></name><xref ref-type="aff" rid="A16">16</xref><xref ref-type="aff" rid="A17">17</xref></contrib><contrib contrib-type="author"><name><surname>Fraser</surname><given-names>Ross M</given-names></name><xref ref-type="aff" rid="A18">18</xref></contrib><contrib contrib-type="author"><name><surname>Kanoni</surname><given-names>Stavroula</given-names></name><xref ref-type="aff" rid="A19">19</xref></contrib><contrib 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rid="A23">23</xref></contrib><contrib contrib-type="author"><name><surname>Pechlivanis</surname><given-names>Sonali</given-names></name><xref ref-type="aff" rid="A24">24</xref></contrib><contrib contrib-type="author"><name><surname>Rayner</surname><given-names>N William</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A12">12</xref></contrib><contrib contrib-type="author"><name><surname>Scott</surname><given-names>Laura J</given-names></name><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Wiltshire</surname><given-names>Steven</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Yengo</surname><given-names>Loic</given-names></name><xref ref-type="aff" rid="A25">25</xref><xref ref-type="aff" rid="A26">26</xref></contrib><contrib contrib-type="author"><name><surname>Kinnunen</surname><given-names>Leena</given-names></name><xref ref-type="aff" rid="A27">27</xref></contrib><contrib contrib-type="author"><name><surname>Rossin</surname><given-names>Elizabeth J</given-names></name><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A5">5</xref><xref ref-type="aff" rid="A28">28</xref><xref ref-type="aff" rid="A29">29</xref></contrib><contrib contrib-type="author"><name><surname>Raychaudhuri</surname><given-names>Soumya</given-names></name><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A30">30</xref><xref ref-type="aff" rid="A31">31</xref></contrib><contrib contrib-type="author"><name><surname>Johnson</surname><given-names>Andrew D</given-names></name><xref ref-type="aff" rid="A32">32</xref></contrib><contrib contrib-type="author"><name><surname>Dimas</surname><given-names>Antigone S</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A33">33</xref><xref ref-type="aff" rid="A34">34</xref></contrib><contrib 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contrib-type="author"><name><surname>Bergman</surname><given-names>Richard N</given-names></name><xref ref-type="aff" rid="A118">119</xref></contrib><contrib contrib-type="author"><name><surname>Tuomilehto</surname><given-names>Jaakko</given-names></name><xref ref-type="aff" rid="A27">27</xref><xref ref-type="aff" rid="A115">116</xref><xref ref-type="aff" rid="A119">120</xref><xref ref-type="aff" rid="A120">121</xref></contrib><contrib contrib-type="author"><name><surname>Boehm</surname><given-names>Bernhard O</given-names></name><xref ref-type="aff" rid="A121">122</xref></contrib><contrib contrib-type="author"><name><surname>Gieger</surname><given-names>Christian</given-names></name><xref ref-type="aff" rid="A22">22</xref></contrib><contrib contrib-type="author"><name><surname>Hveem</surname><given-names>Kristian</given-names></name><xref ref-type="aff" rid="A51">51</xref></contrib><contrib contrib-type="author"><name><surname>Cauchi</surname><given-names>Stephane</given-names></name><xref ref-type="aff" rid="A25">25</xref></contrib><contrib contrib-type="author"><name><surname>Froguel</surname><given-names>Philippe</given-names></name><xref ref-type="aff" rid="A25">25</xref><xref ref-type="aff" rid="A122">123</xref></contrib><contrib contrib-type="author"><name><surname>Baldassarre</surname><given-names>Damiano</given-names></name><xref ref-type="aff" rid="A87">87</xref><xref ref-type="aff" rid="A123">124</xref></contrib><contrib contrib-type="author"><name><surname>Tremoli</surname><given-names>Elena</given-names></name><xref ref-type="aff" rid="A87">87</xref><xref ref-type="aff" rid="A123">124</xref></contrib><contrib contrib-type="author"><name><surname>Humphries</surname><given-names>Steve E</given-names></name><xref ref-type="aff" rid="A124">125</xref></contrib><contrib contrib-type="author"><name><surname>Saleheen</surname><given-names>Danish</given-names></name><xref ref-type="aff" rid="A10">10</xref><xref ref-type="aff" rid="A125">126</xref></contrib><contrib contrib-type="author"><name><surname>Danesh</surname><given-names>John</given-names></name><xref ref-type="aff" rid="A10">10</xref></contrib><contrib contrib-type="author"><name><surname>Ingelsson</surname><given-names>Erik</given-names></name><xref ref-type="aff" rid="A55">55</xref></contrib><contrib contrib-type="author"><name><surname>Ripatti</surname><given-names>Samuli</given-names></name><xref ref-type="aff" rid="A19">19</xref><xref ref-type="aff" rid="A58">58</xref><xref ref-type="aff" rid="A59">59</xref></contrib><contrib contrib-type="author"><name><surname>Salomaa</surname><given-names>Veikko</given-names></name><xref ref-type="aff" rid="A59">59</xref></contrib><contrib contrib-type="author"><name><surname>Erbel</surname><given-names>Raimund</given-names></name><xref ref-type="aff" rid="A126">127</xref></contrib><contrib contrib-type="author"><name><surname>Jöckel</surname><given-names>Karl-Heinz</given-names></name><xref ref-type="aff" rid="A24">24</xref></contrib><contrib contrib-type="author"><name><surname>Moebus</surname><given-names>Susanne</given-names></name><xref ref-type="aff" rid="A24">24</xref></contrib><contrib contrib-type="author"><name><surname>Peters</surname><given-names>Annette</given-names></name><xref ref-type="aff" rid="A86">86</xref></contrib><contrib contrib-type="author"><name><surname>Illig</surname><given-names>Thomas</given-names></name><xref ref-type="aff" rid="A11">11</xref><xref ref-type="aff" rid="A127">128</xref></contrib><contrib contrib-type="author"><name><surname>de Faire</surname><given-names>Ulf</given-names></name><xref ref-type="aff" rid="A70">70</xref></contrib><contrib contrib-type="author"><name><surname>Hamsten</surname><given-names>Anders</given-names></name><xref ref-type="aff" rid="A8">8</xref><xref ref-type="aff" rid="A9">9</xref></contrib><contrib contrib-type="author"><name><surname>Morris</surname><given-names>Andrew D</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>Donnelly</surname><given-names>Peter J</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A128">129</xref></contrib><contrib contrib-type="author"><name><surname>Frayling</surname><given-names>Timothy M</given-names></name><xref ref-type="aff" rid="A53">53</xref></contrib><contrib contrib-type="author"><name><surname>Hattersley</surname><given-names>Andrew T</given-names></name><xref ref-type="aff" rid="A129">130</xref></contrib><contrib contrib-type="author"><name><surname>Boerwinkle</surname><given-names>Eric</given-names></name><xref ref-type="aff" rid="A130">131</xref><xref ref-type="aff" rid="A131">132</xref></contrib><contrib contrib-type="author"><name><surname>Melander</surname><given-names>Olle</given-names></name><xref ref-type="aff" rid="A60">60</xref></contrib><contrib contrib-type="author"><name><surname>Kathiresan</surname><given-names>Sekar</given-names></name><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A5">5</xref><xref ref-type="aff" rid="A132">133</xref></contrib><contrib contrib-type="author"><name><surname>Nilsson</surname><given-names>Peter M</given-names></name><xref ref-type="aff" rid="A60">60</xref></contrib><contrib contrib-type="author"><name><surname>Deloukas</surname><given-names>Panos</given-names></name><xref ref-type="aff" rid="A19">19</xref></contrib><contrib contrib-type="author"><name><surname>Thorsteinsdottir</surname><given-names>Unnur</given-names></name><xref ref-type="aff" rid="A7">7</xref><xref ref-type="aff" rid="A62">62</xref></contrib><contrib contrib-type="author"><name><surname>Groop</surname><given-names>Leif C</given-names></name><xref ref-type="aff" rid="A60">60</xref></contrib><contrib contrib-type="author"><name><surname>Stefansson</surname><given-names>Kari</given-names></name><xref ref-type="aff" rid="A7">7</xref><xref ref-type="aff" rid="A62">62</xref></contrib><contrib contrib-type="author"><name><surname>Hu</surname><given-names>Frank</given-names></name><xref ref-type="aff" rid="A46">46</xref><xref ref-type="aff" rid="A48">48</xref></contrib><contrib contrib-type="author"><name><surname>Pankow</surname><given-names>James S</given-names></name><xref ref-type="aff" rid="A133">134</xref></contrib><contrib contrib-type="author"><name><surname>Dupuis</surname><given-names>Josée</given-names></name><xref ref-type="aff" rid="A32">32</xref><xref ref-type="aff" rid="A40">40</xref></contrib><contrib contrib-type="author"><name><surname>Meigs</surname><given-names>James B</given-names></name><xref ref-type="aff" rid="A6">6</xref><xref ref-type="aff" rid="A134">135</xref></contrib><contrib contrib-type="author"><name><surname>Altshuler</surname><given-names>David</given-names></name><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A5">5</xref><xref ref-type="aff" rid="A6">6</xref><xref ref-type="aff" rid="A135">136</xref><xref ref-type="aff" rid="A136">137</xref><xref ref-type="aff" rid="A137">138</xref><xref ref-type="author-notes" rid="FN4">141</xref></contrib><contrib contrib-type="author"><name><surname>Boehnke</surname><given-names>Michael</given-names></name><xref ref-type="aff" rid="A4">4</xref><xref ref-type="author-notes" rid="FN4">141</xref></contrib><contrib contrib-type="author"><name><surname>McCarthy</surname><given-names>Mark I</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A12">12</xref><xref ref-type="aff" rid="A92">92</xref><xref ref-type="author-notes" rid="FN4">141</xref></contrib><on-behalf-of>for the DIAGRAM Consortium</on-behalf-of></contrib-group><aff id="A1"><label>1</label>Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.</aff><aff id="A2"><label>2</label>Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, USA.</aff><aff id="A3"><label>3</label>University of Pennsylvania - Perelman School of Medicine, Department of Pharmacology, Philadelphia, Pennsylvania, USA.</aff><aff id="A4"><label>4</label>Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA.</aff><aff id="A5"><label>5</label>Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA.</aff><aff id="A6"><label>6</label>Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.</aff><aff id="A7"><label>7</label>deCODE Genetics, Reykjavik, Iceland.</aff><aff id="A8"><label>8</label>Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.</aff><aff id="A9"><label>9</label>Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden.</aff><aff id="A10"><label>10</label>Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.</aff><aff id="A11"><label>11</label>Research Unit of Molecular Epidemiology, Helmholtz Zentrum Muenchen, Neuherberg, Germany.</aff><aff id="A12"><label>12</label>Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.</aff><aff id="A13"><label>13</label>Inserm UMR 1087, Nantes, France.</aff><aff id="A14"><label>14</label>CNRS UMR 6291, Nantes, France.</aff><aff id="A15"><label>15</label>Nantes University, Nantes, France.</aff><aff id="A16"><label>16</label>Estonian Genome Center, University of Tartu, Tartu, Estonia.</aff><aff id="A17"><label>17</label>Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.</aff><aff id="A18"><label>18</label>Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK.</aff><aff id="A19"><label>19</label>Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.</aff><aff id="A20"><label>20</label>MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.</aff><aff id="A21"><label>21</label>Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany.</aff><aff id="A22"><label>22</label>Institute of Genetic Epidemiology, Helmholtz Zentrum Muenchen, Neuherberg, Germany.</aff><aff id="A23"><label>23</label>Department of Medicine I, University Hospital Grosshadern, Ludwig-Maximilians-University, Munich, Germany.</aff><aff id="A24"><label>24</label>Institute for Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, University Duisburg-Essen, Essen, Germany.</aff><aff id="A25"><label>25</label>CNRS-UMR-8199, Institute of Biology and Lille 2 University, Pasteur Institute, Lille, France.</aff><aff id="A26"><label>26</label>University Lille 1, Laboratory of Mathematics, CNRS-UMR 8524, MODAL team, INRIA Lille Nord-Europe, Lille, France.</aff><aff id="A27"><label>27</label>Diabetes Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland.</aff><aff id="A28"><label>28</label>Health Science and Technology MD Program, Harvard University and Massachusetts Institute of Technology, Boston, Massachusetts, USA.</aff><aff id="A29"><label>29</label>Harvard Biological and Biomedical Sciences Program, Harvard University, Boston, Massachusetts, USA.</aff><aff id="A30"><label>30</label>Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.</aff><aff id="A31"><label>31</label>Partners Center for Personalized Genomic Medicine, Boston, Massachusetts, USA.</aff><aff id="A32"><label>32</label>National Heart, Lung, and Blood Institute’s Framingham Heart Study, Framingham, Massachusetts, USA.</aff><aff id="A33"><label>33</label>Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.</aff><aff id="A34"><label>34</label>Biomedical Sciences Research Center Al. Fleming, Vari, Greece.</aff><aff id="A35"><label>35</label>Charles R. Bronfman Institute for Personalized Medicine, Mount Sinai School of Medicine, New York, New York, USA.</aff><aff id="A36"><label>36</label>Child Health and Development Institute, Mount Sinai School of Medicine, New York, New York, USA.</aff><aff id="A37"><label>37</label>Department of Preventive Medicine, Mount Sinai School of Medicine, New York, New York, USA.</aff><aff id="A38"><label>38</label>Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA.</aff><aff id="A39"><label>39</label>Division of Genetics and Endocrinology, Children's Hospital, Boston, Massachusetts, USA.</aff><aff id="A40"><label>40</label>Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA.</aff><aff id="A41"><label>41</label>Diabetes Research Center, Diabetes Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.</aff><aff id="A42"><label>42</label>Division of Endocrinology and Metabolism, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA.</aff><aff id="A43"><label>43</label>Boston University Data Coordinating Center, Boston, Massachusetts, USA.</aff><aff id="A44"><label>44</label>Collaborative Studies Coordinating Center, Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.</aff><aff id="A45"><label>45</label>Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.</aff><aff id="A46"><label>46</label>Department of Nutrition and Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.</aff><aff id="A47"><label>47</label>Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.</aff><aff id="A48"><label>48</label>Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.</aff><aff id="A49"><label>49</label>Saw Swee Hock School of Public Health, National University of Singapore, Singapore.</aff><aff id="A50"><label>50</label>National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.</aff><aff id="A51"><label>51</label>HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger, Norway.</aff><aff id="A52"><label>52</label>Centre for Genetic Epidemiology and Biostatistics, The University of Western Australia, Nedlands, Australia.</aff><aff id="A53"><label>53</label>Genetics of Complex Traits, Institute of Biomedical and Clinical Science, Peninsula Medical School, University of Exeter, Magdalen Road, Exeter, UK.</aff><aff id="A54"><label>54</label>Department of Internal Medicine, Levanger Hospital, Nord-Trøndelag Health Trust, Levanger, Norway.</aff><aff id="A55"><label>55</label>Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.</aff><aff id="A56"><label>56</label>Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.</aff><aff id="A57"><label>57</label>Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.</aff><aff id="A58"><label>58</label>Institute for Molecular Medicine Finland (FIMM), Helsinki, Finland.</aff><aff id="A59"><label>59</label>Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.</aff><aff id="A60"><label>60</label>Lund University Diabetes Centre, Department of Clinical Science Malmö, Scania University Hospital, Lund University, Malmö, Sweden.</aff><aff id="A61"><label>61</label>Institute of Biomedicine, Physiology, University of Eastern Finland, Kuopio Campus, Kuopio, Finland.</aff><aff id="A62"><label>62</label>Faculty of Medicine, University of Iceland, Reykjavík, Iceland.</aff><aff id="A63"><label>63</label>Landspitali University Hospital, Reykjavík, Iceland.</aff><aff id="A64"><label>64</label>Endocrinology-Diabetology Unit, Corbeil-Essonnes Hospital, Corbeil-Essonnes, France.</aff><aff id="A65"><label>65</label>Diabetes Research Centre, Biomedical Research Institute, University of Dundee, Ninewells Hospital, Dundee, UK.</aff><aff id="A66"><label>66</label>Pharmacogenomics Centre, Biomedical Research Institute, University of Dundee, Ninewells Hospital, Dundee, UK.</aff><aff id="A67"><label>67</label>Icelandic Heart Association, Kopavogur, Iceland.</aff><aff id="A68"><label>68</label>Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland.</aff><aff id="A69"><label>69</label>Vaasa Health Care Centre, Vaasa, Finland.</aff><aff id="A70"><label>70</label>Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.</aff><aff id="A71"><label>71</label>Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.</aff><aff id="A72"><label>72</label>Busselton Population Medical Research Institute, Sir Charles Gairdner Hospital, Nedlands, Australia.</aff><aff id="A73"><label>73</label>PathWest Laboratory Medicine of Western Australia, QEII Medical Centre, Nedlands, Australia.</aff><aff id="A74"><label>74</label>School of Pathology and Laboratory Medicine, The University of Western Australia, Nedlands, Australia.</aff><aff id="A75"><label>75</label>School of Population Health, The University of Western Australia, Nedlands, Australia.</aff><aff id="A76"><label>76</label>Department of Pulmonary Physiology and Sleep Medicine, West Australian Sleep Disorders Research Institute, Queen Elizabeth II Medical Centre, Hospital Avenue, Nedlands, Australia.</aff><aff id="A77"><label>77</label>School of Medicine and Pharmacology, University of Western Australia, Nedlands, Australia.</aff><aff id="A78"><label>78</label>Institute of Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.</aff><aff id="A79"><label>79</label>Institute of Human Genetics, University of Bonn, Bonn, Germany.</aff><aff id="A80"><label>80</label>Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.</aff><aff id="A81"><label>81</label>Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, Australia.</aff><aff id="A82"><label>82</label>University General Hospital Attikon, Athens, Greece.</aff><aff id="A83"><label>83</label>South Karelia Central Hospital, Lappeenranta, Finland.</aff><aff id="A84"><label>84</label>UCL Genetics Institute, Department of Genetics, Evolution and Environment, University College London, London, UK.</aff><aff id="A85"><label>85</label>Department of Clinical Chemistry and Central Laboratory, University of Ulm, Ulm, Germany.</aff><aff id="A86"><label>86</label>Institute of Epidemiology II, Helmholtz Zentrum Muenchen, Neuherberg, Germany.</aff><aff id="A87"><label>87</label>Centro Cardiologico Monzino, IRCCS, Milan, Italy.</aff><aff id="A88"><label>88</label>MRC Institute of Genetics and Molecular Medicine at the University of Edinburgh, Western General Hospital, Edinburgh, UK.</aff><aff id="A89"><label>89</label>Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.</aff><aff id="A90"><label>90</label>Netherland Genomics Initiative, Netherlands Consortium for Healthy Ageing and Centre for Medical Systems Biology, Rotterdam, The Netherlands.</aff><aff id="A91"><label>91</label>Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.</aff><aff id="A92"><label>92</label>Oxford National Institute for Health Research Biomedical Research Centre, Churchill Hospital, Oxford, UK.</aff><aff id="A93"><label>93</label>Molecular Medicine, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.</aff><aff id="A94"><label>94</label>Unit of General Practice, Helsinki University General Hospital, Helsinki, Finland.</aff><aff id="A95"><label>95</label>Folkhälsan Research Center, Helsinki, Finland.</aff><aff id="A96"><label>96</label>INSERM CESP U1018, Villejuif, France.</aff><aff id="A97"><label>97</label>University Paris Sud 11, UMRS 1018, Villejuif, France.</aff><aff id="A98"><label>98</label>Department of Medicine, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.</aff><aff id="A99"><label>99</label>Department of Social Services and Health Care, Jakobstad, Finland.</aff><aff id="A100"><label>101</label>Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland, USA.</aff><aff id="A101"><label>102</label>Geriatric Research Education and Clinical Center, Baltimore Veterans Administration Medical Center, Baltimore, Maryland, USA.</aff><aff id="A102"><label>103</label>Program in Personalised and Genomic Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.</aff><aff id="A103"><label>104</label>Department of Medicine/Metabolic Diseases, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.</aff><aff id="A104"><label>105</label>University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge, UK.</aff><aff id="A105"><label>106</label>NIHR Cambridge Biomedical Research Centre, Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge, UK.</aff><aff id="A106"><label>107</label>Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway.</aff><aff id="A107"><label>108</label>Kuopio Research Institute of Exercise Medicine, Kuopio, Finland.</aff><aff id="A108"><label>109</label>Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland.</aff><aff id="A109"><label>110</label>Department of Medical Sciences, Uppsala University, Akademiska Sjukhuset, Uppsala, Sweden.</aff><aff id="A110"><label>111</label>Department of Dietetics-Nutrition, Harokopio University, Athens, Greece.</aff><aff id="A111"><label>112</label>Faculty of Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland.</aff><aff id="A112"><label>113</label>Unit of General Practice, Oulu University Hospital, Oulu, Finland.</aff><aff id="A113"><label>114</label>Finnish Diabetes Association, Tampere, Finland.</aff><aff id="A114"><label>115</label>Pirkanmaa Hospital District, Tampere, Finland.</aff><aff id="A115"><label>116</label>South Ostrobothnia Central Hospital, Seinäjoki, Finland.</aff><aff id="A116"><label>117</label>Department of Medicine, Central Finland Central Hospital, Jyväskylä, Finland.</aff><aff id="A117"><label>118</label>Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA.</aff><aff id="A118"><label>119</label>Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.</aff><aff id="A119"><label>120</label>Red RECAVA Grupo RD06/0014/0015, Hospital Universitario La Paz, Madrid, Spain.</aff><aff id="A120"><label>121</label>Centre for Vascular Prevention, Danube-University Krems, Krems, Austria.</aff><aff id="A121"><label>122</label>Division of Endocrinology and Diabetes, Department of Internal Medicine, University Medical Centre Ulm, Ulm, Germany.</aff><aff id="A122"><label>123</label>Genomic Medicine, Imperial College London, Hammersmith Hospital, London, UK.</aff><aff id="A123"><label>124</label>Department of Pharmacological Sciences, University of Milan, Milan, Italy.</aff><aff id="A124"><label>125</label>Institute of Cardiovascular Science, University College London, London, UK.</aff><aff id="A125"><label>126</label>Center for Non-Communicable Diseases Pakistan, Karachi, Pakistan.</aff><aff id="A126"><label>127</label>Clinic of Cardiology, West German Heart Centre, University Hospital of Essen, University Duisburg-Essen, Essen, Germany.</aff><aff id="A127"><label>128</label>Hannover Unified Biobank, Hannover Medical School, Hannover, Germany.</aff><aff id="A128"><label>129</label>Department of Statistics, University of Oxford, Oxford, UK.</aff><aff id="A129"><label>130</label>Diabetes Genetics, Institute of Biomedical and Clinical Science, Peninsula Medical School, University of Exeter, Exeter, UK.</aff><aff id="A130"><label>131</label>Human Genetics Center, University of Texas Health Science Center at Houston, Houston, Texas, USA.</aff><aff id="A131"><label>132</label>Human Genome Sequencing Center at Baylor College of Medicine, Houston, Texas, USA.</aff><aff id="A132"><label>133</label>Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA.</aff><aff id="A133"><label>134</label>Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, Minnesota, USA.</aff><aff id="A134"><label>135</label>General Medicine Division, Massachusetts General Hospital, Boston, Massachusetts, USA.</aff><aff id="A135"><label>136</label>Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.</aff><aff id="A136"><label>137</label>Department of Molecular Biology, Harvard Medical School, Boston, Massachusetts, USA.</aff><aff id="A137"><label>138</label>Diabetes Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.</aff><author-notes><corresp id="cor1">Correspondence should be addressed to A.P.M. (<email>amorris@well.ox.ac.uk</email>), M.B. (<email>boehnke@umich.edu</email>) or M.I.M. (<email>mark.mccarthy@drl.ox.ac.uk</email>)</corresp><fn id="FN1"><label>100</label><p id="P1">The members of these consortia are listed in the <xref ref-type="supplementary-material" rid="SD2">Supplementary Note</xref>.</p></fn><fn id="FN2" fn-type="deceased"><label>139</label><p id="P2">Deceased.</p></fn><fn id="FN3" fn-type="con"><label>140</label><p id="P3">These authors contributed equally to this work.</p></fn><fn id="FN4"><label>141</label><p id="P4">These authors jointly supervised the work.</p></fn></author-notes><pub-date pub-type="nihms-submitted"><day>23</day><month>7</month><year>2012</year></pub-date><pub-date pub-type="epub"><day>12</day><month>8</month><year>2012</year></pub-date><pub-date pub-type="ppub"><month>9</month><year>2012</year></pub-date><pub-date pub-type="pmc-release"><day>12</day><month>2</month><year>2013</year></pub-date><volume>44</volume><issue>9</issue><fpage>981</fpage><lpage>990</lpage><pmc-comment>elocation-id from pubmed: 10.1038/ng.2383</pmc-comment>
<permissions><license><license-p>Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:
<uri xlink:type="simple" xlink:href="http://www.nature.com/authors/editorial_policies/license.html#terms">http://www.nature.com/authors/editorial_policies/license.html#terms</uri></license-p></license></permissions><abstract><p id="P5">To extend understanding of the genetic architecture and molecular basis of type 2 diabetes (T2D), we conducted a meta-analysis of genetic variants on the Metabochip involving 34,840 cases and 114,981 controls, overwhelmingly of European descent. We identified ten previously unreported T2D susceptibility loci, including two demonstrating sex-differentiated association. Genome-wide analyses of these data are consistent with a long tail of further common variant loci explaining much of the variation in susceptibility to T2D. Exploration of the enlarged set of susceptibility loci implicates several processes, including CREBBP-related transcription, adipocytokine signalling and cell cycle regulation, in diabetes pathogenesis.</p></abstract></article-meta></front><body><p id="P6">Type 2 diabetes (T2D) is a chronic metabolic disease with multifactorial pathogenesis<sup><xref rid="R1" ref-type="bibr">1</xref></sup>. Although the genetic contribution to T2D is well recognized, the current set of 56 established susceptibility loci, identified primarily through large-scale genome-wide association studies (GWAS)<sup><xref rid="R2" ref-type="bibr">2</xref>–<xref rid="R11" ref-type="bibr">11</xref></sup>, captures at best 10% of familial aggregation of the disease. The characteristics (effect sizes and risk allele frequencies (RAF)) of the variants contributing to the “unexplained” genetic variance remain far from clear. At the same time, difficulties in inferring biological mechanisms from the variants of modest effect identified by GWAS have inhibited progress in defining the pathophysiological basis of disease susceptibility. One key question is whether characterization of increasing numbers of risk loci will provide evidence, at the functional level, that susceptibility involves a limited set of molecular processes.</p><p id="P7">To extend the discovery and characterization of variants influencing T2D susceptibility, we performed large-scale genotyping using the Metabochip. This custom array of 196,725 variants was designed to facilitate cost-effective follow-up of nominal associations for T2D and other metabolic and cardiovascular traits, and to enhance fine-mapping of established loci<sup><xref rid="R12" ref-type="bibr">12</xref></sup>. The T2D-nominated component of Metabochip comprises 21,774 variants, including 5,057 “replication” SNPs that capture the strongest, independent (CEU <italic>r</italic><sup>2</sup>< 0.2) autosomal association signals from the GWAS meta-analysis conducted by the DIAbetes Genetics Replication and Meta-analysis (DIAGRAM) Consortium. This genome-wide meta-analysis (“DIAGRAMv3”) includes data from 12,171 cases and 56,862 controls of European descent imputed up to 2.5 million autosomal SNPs, and augments the previously published “DIAGRAMv2” meta-analysis<sup><xref rid="R4" ref-type="bibr">4</xref></sup> with four additional GWAS (<xref ref-type="supplementary-material" rid="SD2">Supplementary Table 1</xref>). The T2D-nominated content of Metabochip includes a further 16,717 variants, most chosen from 1000 Genomes Project pilot data<sup><xref rid="R13" ref-type="bibr">13</xref></sup>, to fine-map 27 established susceptibility loci.</p><sec sec-type="results" id="S1"><title>RESULTS</title><sec id="S2"><title>Study overview</title><p id="P8">Our primary investigation combined the DIAGRAMv3 (“Stage 1”) GWAS meta-analysis with a “Stage 2” meta-analysis comprising 22,669 cases and 58,119 controls genotyped with Metabochip, including 1,178 cases and 2,472 controls of Pakistani descent (PROMIS) (Online Methods and <xref ref-type="supplementary-material" rid="SD2">Supplementary Table 1</xref>). There was little evidence of heterogeneity in allelic effects between European- and Pakistani-descent studies in Stage 2 (<xref ref-type="supplementary-material" rid="SD2">Supplementary Fig. 1</xref>), so we report the combined meta-analysis including PROMIS with genomic control correction.</p></sec><sec id="S3"><title>T2D susceptibility loci reaching genome-wide significance</title><p id="P9">Combining Stage 1 and Stage 2 meta-analyses (<xref ref-type="supplementary-material" rid="SD2">Supplementary Fig. 2</xref>), we identified eight new T2D susceptibility loci at genome-wide significance (<italic>P</italic> < 5 × 10<sup>−8</sup>) (<xref ref-type="table" rid="T1">Table 1</xref>, <xref ref-type="supplementary-material" rid="SD2">Supplementary Fig. 3</xref> and <xref ref-type="supplementary-material" rid="SD1">Supplementary Table 2</xref>). By convention, we have labelled loci according to the gene nearest to the lead SNP, unless a compelling biological candidate maps nearby. The strongest signals mapped to <italic>ZMIZ1</italic> (<italic>P</italic> = 1.0 × 10<sup>−10</sup>), <italic>ANK1</italic> (<italic>P</italic> = 2.5 × 10<sup>−10</sup>), and the region flanking <italic>KLHDC5</italic> (<italic>P</italic> = 6.1 × 10<sup>−10</sup>). We also observed genome-wide significant association at <italic>HMG20A</italic> (<italic>P</italic> = 4.6 × 10<sup>−9</sup>) and <italic>GRB14</italic> (<italic>P</italic> = 1.0 × 10<sup>−8</sup>), both implicated in a recent meta-analysis of T2D in South Asians<sup><xref rid="R10" ref-type="bibr">10</xref></sup>. Neither has previously been reported in European studies, and both remain genome-wide significant after removing PROMIS from the meta-analysis (<italic>HMG20A</italic><italic>P</italic> = 1.9 × 10<sup>−9</sup>; <italic>GRB14</italic><italic>P</italic> = 5.8 × 10<sup>−9</sup>). The lead SNPs from both meta-analyses are in strong linkage disequilibrium (LD) (<italic>HMG20A</italic><italic>r</italic><sup>2</sup> = 0.89 and <italic>GRB14</italic><italic>r</italic><sup>2</sup> = 0.77 in CEU), and likely represent the same association signals. At the previously unreported loci, we observed nominal evidence of association (<italic>P</italic> < 0.05) in the South Asian<sup><xref rid="R10" ref-type="bibr">10</xref></sup> and recent East Asian<sup><xref rid="R11" ref-type="bibr">11</xref></sup> meta-analyses for the lead SNPs at <italic>MC4R</italic> and <italic>ZMIZ1</italic> (<xref ref-type="supplementary-material" rid="SD2">Supplementary Table 3</xref>), with consistent directions of effect across all three ancestry groups.</p><p id="P10">Several of these signals map to loci previously implicated in T2D-related metabolic traits (<xref ref-type="supplementary-material" rid="SD2">Supplementary Table 4</xref>). The lead SNP at <italic>MC4R</italic> is in strong LD with variants associated with BMI<sup><xref rid="R14" ref-type="bibr">14</xref>, <xref rid="R15" ref-type="bibr">15</xref></sup> (CEU <italic>r</italic><sup>2</sup> = 0.80) and triglycerides<sup><xref rid="R16" ref-type="bibr">16</xref></sup> (CEU <italic>r</italic><sup>2</sup> = 0.84) and is associated with waist circumference and insulin resistance<sup><xref rid="R17" ref-type="bibr">17</xref></sup>. As with <italic>FTO</italic>, the T2D-effect at <italic>MC4R</italic> is probably secondary to the BMI association. The lead SNP at <italic>GRB14</italic> is highly correlated with variants associated with waist-hip ratio (WHR)<sup><xref rid="R18" ref-type="bibr">18</xref></sup> and high-density lipoprotein (HDL) cholesterol<sup><xref rid="R16" ref-type="bibr">16</xref></sup> (CEU <italic>r</italic><sup>2</sup> = 0.93). At <italic>CILP2</italic>, the lead SNP for T2D is also associated with triglycerides, low-density lipoprotein (LDL) and total cholesterol<sup><xref rid="R16" ref-type="bibr">16</xref></sup>. In contrast, the previously-reported association signals for haemoglobin A1C (HbA<sub>1C</sub>) levels<sup><xref rid="R19" ref-type="bibr">19</xref></sup> near <italic>ANK1</italic> are both independent (CEU <italic>r</italic><sup>2</sup> < 0.01) of the lead T2D SNP from our meta-analysis. Given the role played by rare <italic>ANK1</italic> mutations in hereditary anemias, the HbA<sub>1C</sub> associations at this locus were assumed to be driven by abnormal erythrocyte development and/or function. However, our newly discovered independent association with T2D (in cohorts where HbA<sub>1C</sub> was not used for diagnosis) suggests that variation at this locus also has direct effects on glucose homeostasis.</p></sec><sec id="S4"><title>Insights into the genetic architecture of T2D</title><p id="P11">The associated lead variants at the eight newly identified loci were common (Stage 2 RAF 0.08–0.89) and had modest effects on T2D susceptibility (allelic odds ratios (OR) 1.07–1.14). Under a multiplicative model within and between variants, the sibling relative risk attributable to lead SNPs rose from λ<sub>S</sub> = 1.093 at the 55 previously described autosomal T2D loci represented on Metabochip (<italic>DUSP9</italic> on chromosome X is not captured) to λ<sub>S</sub> = 1.104 after inclusion of the eight newly discovered loci (<xref ref-type="supplementary-material" rid="SD2">Supplementary Table 5</xref>). Assuming a T2D population prevalence of 8%, these 63 newly discovered and established autosomal loci together account for 5.7% of variance in disease susceptibility, as calculated by transforming dichotomous disease risk onto a continuous liability scale<sup><xref rid="R20" ref-type="bibr">20</xref></sup> (Online Methods).</p><p id="P12">To determine the extent to which additional common variant associations contribute to the overall variance explained, we compared directional consistency in allelic effects between the two stages of the meta-analysis. <xref ref-type="fig" rid="F1">Figure 1</xref> presents the distribution of <italic>Z</italic>-scores from Stage 2, aligned to the risk allele from Stage 1, at a subset of 3,412 independent (CEU <italic>r</italic><sup>2</sup> < 0.05) T2D replication variants that excludes lead SNPs and possible proxies (CEU <italic>r</italic><sup>2</sup> ≥ 0.1) at the 63 newly discovered and established loci represented on Metabochip. The blue curve represents the expected distribution of Stage 2 <italic>Z</italic>-scores under the null hypothesis of no association. There is a clear shift in the observed distribution, corresponding to closer agreement in the direction of allelic effect than expected by chance: 2,172 (69.1%) of the 3,412 SNPs are concordant (binomial test <italic>P</italic> = 2.0 × 10<sup>−104</sup>). For comparison, we examined T2D association patterns in 2,707 independent replication SNPs for QT-interval, the trait showing weakest correlation with T2D susceptibility among those contributing to Metabochip and found far less directional consistency (54.4%, binomial test <italic>P</italic> = 3.3 × 10<sup>−6</sup>). This modest enrichment most likely reflects weak overlap of risk alleles between the two traits, since exclusion of SNPs mapping within 300 kb of directionally consistent T2D replication variants reduced this excess (52.5%, binomial test <italic>P</italic> = 0.060).</p><p id="P13">The observed distribution of <italic>Z</italic>-scores can be considered a mixture of: (i) the “null distribution” of SNPs having no effect on T2D; and (ii) the “alternative distribution” of T2D-associated SNPs (Online Methods). We estimated the features of this alternative distribution (red curve) and noted that addition of this class of SNPs significantly improved the fit to the observed <italic>Z</italic>-scores over the null model. Using simulations, based on parameter estimates from this mixture model, we estimated that 488 (95% confidence interval (CI) 456–521) of the independent replication SNPs, in addition to the 63 newly discovered and established loci, are associated with T2D susceptibility. For comparison, we undertook false-discovery rate (FDR) analysis of the 64,646 SNPs on the Metabochip selected for replication of any trait, using <italic>P</italic>-values from the combined meta-analysis (Online Methods). We observed broad agreement between combined meta-analysis <italic>P</italic>-values, FDR <italic>Q</italic>-values and the posterior probability of alternative distribution membership from the mixture model (<xref ref-type="supplementary-material" rid="SD2">Supplementary Fig. 4</xref>).</p><p id="P14">We were concerned that these additional, weaker association signals might reflect subtle stratification effects not eliminated by genomic control correction. However, using diverse European populations from the 1000 Genomes Project<sup><xref rid="R13" ref-type="bibr">13</xref></sup> (Online Methods), we found no evidence that directionally-consistent T2D replication SNPs differed from other Metabochip replication SNPs with respect to <italic>F<sub>ST</sub></italic> (<italic>P</italic> = 0.88).</p><p id="P15">As expected, the estimated allelic ORs of the 488 SNPs are modest (1.01–1.11 in Stage 2), and larger samples would be required to establish association at genome-wide significance. For example, by simulating an additional 100,000 T2D cases and 100,000 controls as a “third stage” to the combined meta-analysis, we calculate that only <sup>~</sup>37% of the 488 replication SNPs in the alternative distribution would achieve this threshold. We estimate that these variants jointly account for λ<sub>S</sub> = 1.088 (95% CI 1.083–1.094), increasing the overall liability-scale variance explained to 10.7% (10.4–11.0%).</p></sec><sec id="S5"><title>Additional sources of variation contributing to susceptibility</title><p id="P16">These estimates likely set a lower bound to the overall liability-scale variance attributable to common SNPs. The mixture model does not take account loci not represented by Metabochip T2D replication SNPs due to failures in array design or manufacture or because the association signal in DIAGRAMv3 was too weak to merit inclusion. Indeed, the latter applied to two of the genome-wide significant loci, <italic>ANKRD55</italic> and <italic>GRB14</italic>, which were nominated for inclusion on Metabochip because of associations with WHR (<italic>ANKRD55</italic> and <italic>GRB14</italic>), blood pressure (<italic>ANKRD55</italic>) and plasma lipid concentrations (<italic>GRB14</italic>), rather than T2D.</p><p id="P17">To estimate the contribution to the variance explained by common variants genome-wide, we undertook polygenic mixed linear modelling analyses using GCTA<sup><xref rid="R21" ref-type="bibr">21</xref>, <xref rid="R22" ref-type="bibr">22</xref></sup> in two DIAGRAMv3 GWAS data sets: DGI (1,022 cases, 1,075 controls) and WTCCC (1,924 cases, 2,938 controls). The estimated liability-scale variance explained by the full set of GWAS SNPs was consistent between the two studies: 62.6% for DGI (95% CI 38.1–87.1%) and 63.9% for WTCCC (95% CI 52.1–75.8%). These results are similar to those obtained from a complementary method integrating polygenic risk score analysis and approximate Bayesian computation<sup><xref rid="R23" ref-type="bibr">23</xref></sup> applied to the DIAGRAMv2 meta-analysis<sup><xref rid="R4" ref-type="bibr">4</xref></sup>, which estimated that <sup>~</sup>49% of liability-scale variance was explained by common variants genome-wide. These data indicate that a substantial proportion of the variation in T2D risk is captured by common variant association signals that, individually, lie beyond unequivocal detection in single SNP analyses.</p><p id="P18">The DIAGRAMv2 meta-analysis<sup><xref rid="R4" ref-type="bibr">4</xref></sup> had provided some evidence for loci harboring multiple independent association signals. To understand the extent to which additional variance might be attributable to multiple variants at established and newly discovered loci, we extended these analyses, focusing on the detection of independent (CEU <italic>r</italic><sup>2</sup> < 0.05) association signals that lie outside the recombination interval containing the lead SNP (<xref ref-type="supplementary-material" rid="SD1">Supplementary Table 2</xref>). We detected two loci at which multiple independent association signals attained genome-wide significance: <italic>KCNQ1</italic> (rs163184, <italic>P</italic> = 1.2 × 10<sup>−11</sup>; rs231361, <italic>P</italic> = 1.2 × 10<sup>−9</sup>; CEU <italic>r</italic><sup>2</sup> = 0.01) and <italic>CDKN2A/B</italic> (rs10811661, <italic>P</italic> = 3.7 × 10<sup>−27</sup>; rs944801, <italic>P</italic> = 2.4 × 10<sup>−9</sup>; CEU <italic>r</italic><sup>2</sup> = 0.01) (<xref ref-type="fig" rid="F2">Fig. 2</xref>). Both signals at <italic>KCNQ1</italic> have previously been reported in East Asian and European populations<sup><xref rid="R4" ref-type="bibr">4</xref>,<xref rid="R24" ref-type="bibr">24</xref></sup>. However, the secondary signal at <italic>CDKN2A/B</italic>, which maps to the non-coding <italic>CDKN2B-AS1</italic> (<italic>ANRIL</italic>) transcript, has not previously been implicated in T2D susceptibility. This signal is independent of the previously reported haplotype effect at the primary T2D signal at this locus, which is itself likely due to the phase relationships between two clades of partially correlated variants<sup><xref rid="R25" ref-type="bibr">25</xref>,<xref rid="R26" ref-type="bibr">26</xref></sup>. We also observed putative independent associations (<italic>P</italic> < 10<sup>−5</sup>) at <italic>DGKB</italic> (rs17168486, <italic>P</italic> = 5.9 × 10<sup>−11</sup>; rs6960043, <italic>P</italic> = 3.4 × 10<sup>−7</sup>; CEU <italic>r</italic><sup>2</sup> = 0.01) and <italic>MC4R</italic> (rs12970134, <italic>P</italic> = 1.2 × 10<sup>−8</sup>; rs11873305, <italic>P</italic> = 3.8 × 10<sup>−7</sup>; CEU <italic>r</italic><sup>2</sup> = 0.02). These results suggest that multiple independent association signals are widespread at T2D susceptibility loci. Imputation up to the more complete reference panels emerging from the 1000 Genomes Project<sup><xref rid="R13" ref-type="bibr">13</xref></sup> and recently developed approaches that support approximate conditional analyses using meta-analysis summary level data<sup><xref rid="R27" ref-type="bibr">27</xref></sup> will be important tools for documenting the full extent of such effects, especially where the variants map to the same recombination interval.</p><p id="P19">It has been argued that common variant association signals will often reflect unobserved causal alleles of lower frequency and greater effect size<sup><xref rid="R28" ref-type="bibr">28</xref></sup>. The fine-mapping content of Metabochip allowed us to seek empirical evidence to support this “synthetic association” hypothesis. We estimate, using 1000 Genomes Project data<sup><xref rid="R13" ref-type="bibr">13</xref></sup> applied to HapMap CEU samples, that the array captures (CEU <italic>r</italic><sup>2</sup> ≥ 0.8) 89.6% of common SNPs (minor allele frequency (MAF) ≥ 5%) and 60.0% of low-frequency variants (1% ≤ MAF < 5%) across Metabochip fine-mapping regions<sup><xref rid="R12" ref-type="bibr">12</xref></sup>. This represents a substantial improvement over HapMap<sup><xref rid="R29" ref-type="bibr">29</xref>, <xref rid="R30" ref-type="bibr">30</xref></sup> which, across the same regions, captures 76.8% and 32.4% of common and low-frequency variants, respectively.</p><p id="P20">Across 36 fine-mapping regions on Metabochip that contain T2D susceptibility loci (including 27 explicitly chosen by DIAGRAM), we compared the characteristics of previously reported lead SNPs (defined by GWAS and HapMap imputation) and those emerging from the Stage 2 Metabochip meta-analysis. We restricted these comparisons to Stage 2 to avoid penalizing low-frequency variants not typed or well-imputed in Stage 1. The GWAS and Metabochip lead SNPs were the same, or highly-correlated (CEU <italic>r</italic><sup>2</sup> > 0.8), at 20 loci (15 with CEU <italic>r</italic><sup>2</sup> > 0.95) (<xref ref-type="supplementary-material" rid="SD2">Supplementary Table 6</xref>). The low LD between GWAS and Metabochip lead SNPs at <italic>DGKB</italic> and <italic>KCNQ1</italic> (both CEU <italic>r</italic><sup>2</sup> = 0.00) arises because they “switch” between independent association signals at these loci (<xref ref-type="fig" rid="F2">Fig. 2</xref>). For the remaining 14 loci, there was only modest LD between the previously reported GWAS and Metabochip-defined lead SNPs (CEU <italic>r</italic><sup>2</sup> between 0.06 and 0.77). However, at only two loci did the lead SNP after Metabochip fine-mapping have substantially lower MAF and higher OR than the previously reported GWAS lead SNP: <italic>PROX1</italic> (rs17712208, MAF = 0.03, OR = 1.20; rs340874, MAF = 0.48, OR = 1.06) and <italic>KLF14</italic> (7-130116320, MAF = 0.02, OR = 1.10; rs972283, MAF = 0.48, OR = 1.01). Since coverage across Metabochip fine-mapping regions is incomplete, we cannot unequivocally exclude the presence of causal low-frequency alleles at any single locus. However, the paucity of low-frequency candidate alleles across 36 loci suggests that most causal variants at these loci are common. A contribution of even rarer causal alleles (too rare to be represented on Metabochip) is also unlikely because the substantial effect sizes required to drive common variant association signals are inconsistent with the modest familial aggregation of T2D<sup><xref rid="R23" ref-type="bibr">23</xref></sup>. This interpretation, favoring common causal alleles, is in agreement with the observed consistency of T2D risk variant associations across major ancestry groups<sup><xref rid="R31" ref-type="bibr">31</xref></sup>.</p></sec><sec id="S6"><title>Sex-differentiated analyses</title><p id="P21">We performed sex-differentiated meta-analysis<sup><xref rid="R32" ref-type="bibr">32</xref></sup> (Online Methods and <xref ref-type="supplementary-material" rid="SD2">Supplementary Figs. 5 and 6</xref>) to test for association of each SNP with T2D, allowing for heterogeneity in allelic effects between males (20,219 cases, 54,604 controls) and females (14,621 cases, 60,377 controls), thereby identifying two additional loci achieving genome-wide significance (<xref ref-type="table" rid="T2">Table 2</xref> and <xref ref-type="supplementary-material" rid="SD2">Supplementary Table 7</xref>). The association signal mapping near <italic>CCND2</italic> is most significant in males (male <italic>P</italic> = 1.1 × 10<sup>−9</sup>, female <italic>P</italic> = 0.036, heterogeneity <italic>P</italic> = 0.013), while that upstream of <italic>GIPR</italic> is most significant in females (female <italic>P</italic> = 2.2 × 10<sup>−7</sup>, male <italic>P</italic> = 0.0037, heterogeneity <italic>P</italic> = 0.057) (<xref ref-type="supplementary-material" rid="SD2">Supplementary Fig. 7</xref>). The lead sex-differentiated SNP in <italic>GIPR</italic> is only weakly correlated with previously reported associations with BMI<sup><xref rid="R15" ref-type="bibr">15</xref></sup> (CEU <italic>r</italic><sup>2</sup> = 0.06) and two-hour glucose levels<sup><xref rid="R33" ref-type="bibr">33</xref></sup> (CEU <italic>r</italic><sup>2</sup> = 0.07) (<xref ref-type="supplementary-material" rid="SD2">Supplementary Table 4</xref>).</p><p id="P22">The sex-differentiated analyses also revealed nominal evidence of heterogeneity (<italic>P</italic> < 0.05) at four established T2D susceptibility loci (<xref ref-type="table" rid="T2">Table 2</xref> and <xref ref-type="supplementary-material" rid="SD2">Supplementary Tables 7 and 8</xref>): <italic>KCNQ1</italic> (<italic>P</italic> = 0.0013), <italic>DGKB</italic> (<italic>P</italic> = 0.0068) and <italic>BCL11A</italic> (<italic>P</italic> = 0.012) were most significantly associated in males, and <italic>GRB14</italic> (<italic>P</italic> = 0.0080) in females. The sex-differentiated association at <italic>GRB14</italic> is consistent with the female-specific effect on WHR observed at this locus<sup><xref rid="R18" ref-type="bibr">18</xref></sup>. As <italic>KCNQ1</italic> and <italic>DGKB</italic> demonstrate multiple independent associations in the sex-combined meta-analysis, we investigated whether sex differences in allelic effects were consistent across these signals (<xref ref-type="supplementary-material" rid="SD2">Supplementary Fig. 8</xref>). This appeared true for <italic>DGKB</italic> (rs17168486, male <italic>P</italic> = 6.5 × 10<sup>−13</sup>, female <italic>P</italic> = 0.0052; rs6960043, male <italic>P</italic> = 7.9 × 10<sup>−7</sup>, female <italic>P</italic> = 0.015), but not <italic>KCNQ1</italic> (rs163184, male <italic>P</italic> = 8.5 × 10<sup>−15</sup>, female <italic>P</italic> = 7.8 × 10<sup>−3</sup>; rs231361, male <italic>P</italic> = 2.9 × 10<sup>−6</sup>, female <italic>P</italic> = 2.9 × 10<sup>−6</sup>).</p></sec><sec id="S7"><title>Understanding the biology of T2D susceptibility loci</title><p id="P23">For most T2D susceptibility loci, the underlying causal variants and the genes through which they act are yet to be identified, and the pathophysiological processes mediating disease risk remain unclear. We applied a variety of approaches to the newly discovered and established T2D susceptibility loci, and in some cases to putative loci with more modest evidence of association, to identify mechanisms involved in disease pathogenesis.</p></sec><sec id="S8"><title>Physiological analyses</title><p id="P24">As noted earlier, lead SNPs at several newly identified loci are in strong LD with variants associated with other T2D-related metabolic traits. To gain a more complete picture of patterns of trait overlap, we first assessed the effect of T2D risk alleles on glycemic traits in European-descent meta-analyses from the MAGIC Investigators (Online Methods). Fasting glucose associations were analyzed for up to 133,010 non-diabetic individuals with GWAS and/or Metabochip data<sup><xref rid="R34" ref-type="bibr">34</xref></sup>. In addition to the nine loci previously reported (<italic>MTNR1B, DGKB, ADCY5, PROX1, GCK, GCKR, TCF7L2, SLC30A8 and C2CD4A</italic>)<sup><xref rid="R4" ref-type="bibr">4</xref>,<xref rid="R5" ref-type="bibr">5</xref></sup>, four more T2D association signals were genome-wide significant for fasting glucose: <italic>CDKN2A/B</italic> (<italic>P</italic> = 5.7 × 10<sup>−18</sup>), <italic>ARAP1</italic> (<italic>P</italic> = 1.2 × 10<sup>−10</sup>), <italic>IGF2BP2</italic> (<italic>P</italic> = 1.8 × 10<sup>−8</sup>) and <italic>CDKAL1</italic> (<italic>P</italic> = 2.0 × 10<sup>−8</sup>) (<xref ref-type="supplementary-material" rid="SD2">Supplementary Table 9</xref>). The <italic>ZBED3</italic> locus also attained genome-wide significance with fasting glucose after adjustment for BMI (<italic>P</italic> = 1.2 × 10<sup>−8</sup>). In contrast, lead T2D SNPs at 27 of the newly discovered and established loci showed no evidence of association with fasting glucose (<italic>P</italic><italic>></italic> 0.05), despite sample sizes ranging from 38,424 to 132,999 individuals (<xref ref-type="supplementary-material" rid="SD2">Supplementary Table 10 and Supplementary Fig. 9</xref>). Lead T2D SNPs at the remaining 24 loci were nominally associated with fasting glucose (<italic>P</italic> < 0.05), all with directionally consistent effects. These data extend previous reports indicating that the genetic landscape of pathological and physiological variation in glycemia is only partially overlapping, and are consistent with reciprocal analyses reported in the companion MAGIC paper<sup><xref rid="R34" ref-type="bibr">34</xref></sup>.</p><p id="P25">Second, we extended our previous analysis<sup><xref rid="R4" ref-type="bibr">4</xref></sup> of the physiological consequences of T2D risk alleles to include the newly identified loci. We used the published MAGIC meta-analysis (up to 37,037 non-diabetic individuals) of HOMA indices of beta-cell function and insulin sensitivity<sup><xref rid="R5" ref-type="bibr">5</xref></sup> as these traits were not included in the enlarged Metabochip study<sup><xref rid="R34" ref-type="bibr">34</xref></sup>. The risk allele at <italic>ANK1</italic> has features (nominally significant reduction in HOMA-B) indicating a primary effect on beta-cell function, whereas those at <italic>GRB14</italic> and <italic>AKNRD55</italic> are characteristic of loci acting primarily through insulin resistance (increased HOMA-IR) (<xref ref-type="supplementary-material" rid="SD2">Supplementary Fig. 10 and Supplementary Table 10</xref>). The results for <italic>GRB14</italic> are consistent with its broad impact on insulin-resistance related traits (described below), while at <italic>AKNRD55</italic>, these analyses point to <italic>MAP3K1</italic>, encoding MEK kinase, a key component of the insulin-signalling pathway, as the stand-out local candidate.</p><p id="P26">Next, we examined the effect of T2D risk alleles on anthropometric and lipid traits using data from the GIANT Consortium (up to 119,600 individuals after excluding data from T2D case series)<sup><xref rid="R15" ref-type="bibr">15</xref></sup> and the Global Lipids Genetics Consortium (up to 100,184 individuals)<sup><xref rid="R16" ref-type="bibr">16</xref></sup> (Online Methods and <xref ref-type="supplementary-material" rid="SD2">Supplementary Tables 11 and 12</xref>). The only lead SNP to demonstrate convincing evidence of association (<italic>P</italic> < 10<sup>−5</sup>) with adiposity was at <italic>MC4R</italic>. The lead SNPs at <italic>MC4R</italic> and <italic>GRB14</italic> show the same pattern of lipid associations (<italic>P</italic> < 10<sup>−5</sup>): reduced HDL and raised triglycerides. In contrast, the lipid associations at <italic>CILP2</italic> and <italic>GIPR</italic> ran counter to expected epidemiological correlations: T2D risk alleles were associated with reduced triglyceride levels at both loci, and at <italic>CILP2</italic> with reduced LDL and total cholesterol.</p><p id="P27">Finally, we noticed that the lead T2D SNP at the <italic>BCAR1</italic> locus is genome-wide significant for type 1 diabetes (T1D)<sup><xref rid="R35" ref-type="bibr">35</xref></sup>, although risk is conferred by the opposite alleles. Across 37 T1D susceptibility loci (<xref ref-type="supplementary-material" rid="SD2">Supplementary Fig. 11</xref>), we observed nominal evidence (<italic>P</italic> < 0.05) of association to T2D at six. For three of these (<italic>BCAR1</italic>, <italic>GLIS3</italic> and <italic>RAD51L1</italic>), the T1D risk allele was protective for T2D, while at the others (<italic>C6orf173</italic>, <italic>COBL</italic> and <italic>C10orf59</italic>), the effects were coincident. These data indicate that rates of diagnostic misclassification among T2D cases in our study are low, and also highlight interesting points of overlap in the processes involved in risk of, and protection from, these two major forms of diabetes.</p></sec><sec id="S9"><title>Mapping potential causal transcripts and variants</title><p id="P28">The T2D-association signals emerging from the present meta-analysis map to regions containing many transcripts and potential functional variants. To identify promising regional transcripts, we examined expression quantitative trait locus (eQTL) data from a variety of tissues (Online Methods and <xref ref-type="supplementary-material" rid="SD2">Supplementary Note</xref>). At six of the newly discovered loci, the lead T2D SNP showed strong <italic>cis</italic>-eQTL associations and was highly correlated (CEU <italic>r</italic><sup>2</sup> > 0.8) with the lead <italic>cis</italic>-eQTL SNP (<xref ref-type="supplementary-material" rid="SD2">Supplementary Table 13</xref>). These “coincident” eQTL implicate <italic>GRB14</italic> (omental fat), <italic>ANK1</italic> (omental and subcutaneous fat, liver and prefrontal cortex), <italic>KLHDC5</italic> (blood, T cells and CD4+ lymphocytes), <italic>BCAR1</italic> (blood), <italic>ATP13A1</italic> (at the <italic>CILP2</italic> locus, blood and monocytes), <italic>HMG20A</italic> (liver) and <italic>LINGO1</italic> (also at the <italic>HMG20A</italic> locus, adipose tissue). For those loci (<italic>GRB14</italic>, <italic>ANK1</italic> and <italic>BCAR1</italic>) for which individual-level expression data for the appropriate tissues were available<sup><xref rid="R36" ref-type="bibr">36</xref></sup>, we confirmed signal coincidence by conditional analyses (<xref ref-type="supplementary-material" rid="SD2">Online Methods and Supplementary Table 14</xref>).</p><p id="P29">We used 1000 Genomes Project data<sup><xref rid="R13" ref-type="bibr">13</xref></sup> to search for non-synonymous variants in strong LD (CEU <italic>r</italic><sup>2</sup> > 0.8) with lead SNPs at the newly discovered loci (Online Methods). The only candidate allele uncovered was a non-synonymous variant in exon 6 of <italic>TM6SF2</italic> (19-19379549, CEU <italic>r</italic><sup>2</sup> = 0.98 with rs10401969) at the <italic>CILP2</italic> locus. This change is predicted by SIFT<sup><xref rid="R37" ref-type="bibr">37</xref></sup> to have no appreciable effect on protein function.</p></sec><sec id="S10"><title>Pathway and protein-protein interaction analyses</title><p id="P30">To extend previous efforts to define pathways and networks involved in T2D pathogenesis<sup><xref rid="R4" ref-type="bibr">4</xref></sup>, we combined meta-analysis data with protein-protein interactions (PPI), semantic relationships within the published literature and annotated pathways (<xref ref-type="fig" rid="F3">Fig. 3</xref>). For these analyses, we generated a “primary” list of 77 transcripts mapping nearest to lead SNPs at T2D susceptibility loci or implicated in monogenic diabetes<sup><xref rid="R38" ref-type="bibr">38</xref></sup> (Online Methods and <xref ref-type="supplementary-material" rid="SD2">Supplementary Table 15</xref>).</p><p id="P31">Using a refined database of high-confidence PPI<sup><xref rid="R39" ref-type="bibr">39</xref>, <xref rid="R40" ref-type="bibr">40</xref></sup>, we constructed a network of 314 proteins from these 77 transcripts using DAPPLE<sup><xref rid="R41" ref-type="bibr">41</xref></sup>. We detected an excess of physical interactions in the network, both direct (between the associated transcripts themselves, <italic>P</italic> < 10<sup>−4</sup>) and indirect (via 237 shared interactors not on the list of associated transcripts, <italic>P</italic> = 0.0070). There was no evidence that this set of shared interactors was enriched for T2D-associated variants. Some interactions, such as those between the potassium channel encoding genes <italic>KCNJ11</italic> and <italic>ABCC8</italic>, are expected, while other sub-networks are of greater novelty. For example, the transcriptional co-activator protein <italic>CREBBP</italic>, implicated in the coupling of chromatin remodelling to transcription factor recognition, does not map to any T2D susceptibility locus. However, it is the most connected gene for protein-level interactions (<italic>P</italic> < 0.005) in the PPI network, interacting with nine primary transcripts, eight implicated in monogenic diabetes or mapping to established T2D susceptibility loci (<italic>HNF1A, HNF1B, HNF4A, PLAGL1, TCF7L2, PPARG, PROX1</italic> and <italic>NOTCH2</italic>) and one from a locus with a strong, but not genome-wide significant, association (<italic>ETS1</italic>, lead SNP rs7931302, <italic>P</italic> = 3.8 × 10<sup>−7</sup>). Other shared interactors identified through these analyses included <italic>SERTAD1, FOXO1, PPARGC1A, GRB10</italic> and <italic>MAFA</italic>. Several of these play roles in the transcriptional regulation of diabetes-relevant tissues, and some also interact with <italic>CREBBP</italic>. We used a pre-defined set of 1,814 genes encoding “DNA-binding proteins” (Online Methods) to show that: (i) T2D signals are highly enriched for transcription factors (21 of 71 primary transcripts listed within the HGNC catalog, compared to 1,793 of 19,162, <italic>P</italic> = 2.3 × 10<sup>−6</sup>); and (ii) transcription factors within T2D loci are enriched for interaction with <italic>CREBBP</italic> (taking the 1,164 listed in the protein interaction database, 9 of 21 compared with 127 of 1,143, <italic>P</italic> = 2.7 × 10<sup>−4</sup>). These data suggest that modulation of CREBBP-binding transcription factors plays an important role in T2D susceptibility.</p><p id="P32">The same set of 77 primary transcripts showed modest evidence of excess connectivity (<italic>P</italic> = 0.020 by permutation) using text-mining approaches<sup><xref rid="R42" ref-type="bibr">42</xref></sup> (Online Methods). When we used this set of 77 genes as a “seed” to query a list of 77 “secondary” transcripts (nearest to lead SNPs with posterior probability of T2D-association > 75% from the mixture model) (<xref ref-type="supplementary-material" rid="SD2">Supplementary Table 15</xref>), we found significant connections (<italic>P</italic> < 0.001) between the primary associated transcripts and four other genes: <italic>LEPR</italic> (leptin obesity pathways), <italic>MYC</italic> (cell-cycle pathway), <italic>GATA6</italic> (pancreas development pathway) and <italic>DLL4</italic> (Notch signalling target).</p><p id="P33">We also tested for enrichment of GWAS associated transcripts in pathway data. To retain power, we focused on 16 biological hypotheses chosen for assumed relevance to T2D pathogenesis<sup><xref rid="R4" ref-type="bibr">4</xref>,<xref rid="R43" ref-type="bibr">43</xref>–<xref rid="R45" ref-type="bibr">45</xref></sup> (<xref ref-type="supplementary-material" rid="SD2">Supplementary Note</xref>). We used a two-step modified gene-set enrichment analysis (GSEA) approach applied sequentially to Stage 1 (using MAGENTA<sup><xref rid="R46" ref-type="bibr">46</xref></sup>) and Stage 2 meta-analyses (Online Methods and <xref ref-type="supplementary-material" rid="SD2">Supplementary Table 16</xref>). Of the 16 biological hypotheses tested, two demonstrated reproducible enrichment of T2D associations. The strongest enrichment was observed for a broader set of primary and secondary transcripts mapping to T2D-associated loci in the adipocytokine signalling pathway (MAGENTA <italic>P</italic> = 6.2 × 10<sup>−5</sup>; modified GSEA <italic>P</italic> = 1.6 × 10<sup>−4</sup>). This gene set includes the adiponectin, leptin and TNF-alpha signalling pathways previously implicated in the development of insulin resistance<sup><xref rid="R47" ref-type="bibr">47</xref></sup>, but for which genome-wide significant common variant associations with T2D susceptibility have not been previously reported. This analysis highlighted eight genes in this pathway most likely to be causal for T2D susceptibility: <italic>IRS1, LEPR, RELA, RXRG, ACSL1, NFKB1, CAMKK1</italic> and a monogenic diabetes gene <italic>AKT2</italic>. Members of this pathway were also strongly represented (17 out of 314) in the DAPPLE PPI network (<italic>P</italic> = 7.5 × 10<sup>−14</sup>). Modest but robust enrichment was also observed for genes influencing cell cycle, in particular regulators of the G1 phase during mitosis (MAGENTA <italic>P</italic> = 2.0 × 10<sup>−4</sup>; modified GSEA <italic>P</italic> = 3.0 × 10<sup>−3</sup>). The majority of genes driving these cell-cycle enrichments were cyclin-dependent kinase (CDK) inhibitors (<italic>CDKN2A/B, CDKN1C</italic> and <italic>CDKN2C</italic>) and cyclins that activate CDKs (<italic>CCNE2, CCND2</italic> and <italic>CCNA2</italic>). Many of these regulate <italic>CDK4</italic> or <italic>CDK6</italic>, which are known to play a role in pancreatic beta-cell proliferation<sup><xref rid="R48" ref-type="bibr">48</xref>, <xref rid="R49" ref-type="bibr">49</xref></sup>. We saw no evidence of enrichment for other processes implicated in T2D pathogenesis, including amyloid formation, ER stress and insulin signalling.</p></sec></sec><sec sec-type="discussion" id="S11"><title>DISCUSSION</title><p id="P34">We have expanded T2D association analysis to almost 150,000 individuals. In so doing, we have added another 10 loci to the list of confirmed common variant signals: for several of these, we have identified strong positional candidates based on expression data and known biology. The data support the view that much of the overall variance in T2D susceptibility can be attributed to the impact of a large number of common causal variants, most of very modest effect. While such a model poses challenges for accumulating genome-wide significant evidence of association at a specific variant, it does suggest that genetic profiling based on the entirety of sequence variation has the potential to provide useful risk stratification for T2D.</p><p id="P35">If common causal alleles explain a substantial component of T2D susceptibility, the contribution of rare and low-frequency risk variants may be less than is often assumed: re-sequencing studies will soon provide empirical data to address this question. In particular, it will be important to determine whether, as the number of susceptibility loci increases, there is evidence that the pathophysiological mechanisms implicated by human genetics coalesce around a limited set of core pathways and networks. Our data suggest that this may be the case, with a variety of analytical approaches pointing to cell cycle regulation, adipocytokine signalling and CREBBP-related transcription factor activity as key processes involved in T2D pathogenesis.</p></sec><sec sec-type="methods" id="S12"><title>ONLINE METHODS</title><sec id="S13"><title>Stage 1 meta-analysis</title><p id="P36">The Stage 1 meta-analysis consisted of 12,171 T2D cases and 56,862 controls across 12 GWAS from European descent populations (<xref ref-type="supplementary-material" rid="SD2">Supplementary Table 1</xref>). Samples were typed with a range of GWAS genotyping products. Sample and SNP quality control (QC) were undertaken within each study. Each GWAS was then imputed at up to 2.5 million SNPs using CEU samples from Phase II of the International HapMap Project<sup><xref rid="R28" ref-type="bibr">28</xref></sup>. Each SNP with MAF > 1% passing QC was tested for association with T2D under an additive model after adjustment for study-specific covariates, including indicators of population structure. The results of each GWAS were corrected for residual population structure using the genomic control inflation factor<sup><xref rid="R50" ref-type="bibr">50</xref></sup> and were combined via fixed-effects inverse-variance weighted meta-analysis. The results of the Stage 1 meta-analysis were subsequently corrected by genomic control (λ<sub>GC</sub> = 1.10).</p></sec><sec id="S14"><title>Stage 2 meta-analysis</title><p id="P37">The Stage 2 meta-analysis consisted of 21,491 T2D cases and 55,647 controls across 25 studies from European descent populations and 1,178 T2D cases and 2,472 controls from one study of Pakistani descent (PROMIS) (<xref ref-type="supplementary-material" rid="SD2">Supplementary Table 1</xref>). All samples were genotyped with Metabochip. Sample and SNP QC were undertaken within each study. Each SNP with MAF > 1% passing QC was tested for association with T2D under an additive model after adjustment for study-specific covariates. We would expect inflation in association signals across the content of Metabochip, even in the absence of population structure, because it has been designed to be enriched for T2D and other T2D-related metabolic trait loci. The results of each study were thus corrected for residual population structure using the genomic control inflation factor obtained from a subset of 3,598 independent “QT-interval” SNPs (CEU <italic>r</italic><sup>2</sup> < 0.05), which were not expected to be associated with T2D. The Stage 2 meta-analysis was performed in two steps: (i) combine all studies of European descent; and (ii) add the PROMIS study. In both steps, the results of each study were combined via fixed-effects inverse-variance weighted meta-analysis. The results of the Stage 2 European meta-analysis were corrected by “QT-interval” genomic control (λ<sub>QT</sub> = 1.19), but this adjustment was not then necessary after the addition of PROMIS (λ<sub>QT</sub> = 0.99 was less than 1). Heterogeneity in allelic effects between European descent studies and subsequently between the European meta-analysis and PROMIS was assessed by means of Cochran’s <italic>Q</italic>-statistic<sup><xref rid="R51" ref-type="bibr">51</xref></sup>.</p></sec><sec id="S15"><title>Combined meta-analysis</title><p id="P38">The results of the Stage 1 and Stage 2 meta-analyses were combined for all Metabochip SNPs via fixed-effects inverse-variance weighted meta-analysis. The combined meta-analysis consisted of 34,840 cases and 114,981 controls. This was performed in two steps: (i) combine Stage 1 meta-analysis with European descent Stage 2 meta-analysis; and (ii) add the PROMIS study. The results of the combined European meta-analysis was corrected by “QT-interval” genomic control (λ<sub>QT</sub> = 1.13), but this adjustment was not necessary after the addition of PROMIS (λ<sub>QT</sub> = 0.98 was less than 1) (<xref ref-type="supplementary-material" rid="SD2">Supplementary Fig. 12</xref>). Heterogeneity in allelic effects between the Stage 1 and Stage 2 meta-analyses was assessed by means of Cochran’s <italic>Q</italic>-statistic.</p></sec><sec id="S16"><title>Look-up of meta-analysis results for lead SNPs in GWAS of South and East Asian descent</title><p id="P39">We obtained summary statistics (RAFs, association <italic>P</italic>-values, allelic ORs and 95% CIs) for lead SNPs at the newly discovered loci in meta-analyses of T2D GWAS in: (i) 5,561 cases and 14,458 controls of South Asian descent<sup><xref rid="R10" ref-type="bibr">10</xref></sup>, excluding 1,958 overlapping samples from PROMIS that were also included in our study, comprising 568,976 directly genotyped autosomal SNPs; and (ii) 6,952 cases and 11,865 controls of East Asian descent<sup><xref rid="R11" ref-type="bibr">11</xref></sup>, comprising 2,626,356 directly genotyped and imputed autosomal SNPs. For each SNP, summary statistics were aligned to the risk allele in our primarily European descent meta-analysis.</p></sec><sec id="S17"><title>Calculation of sibling relative risk and liability-scale variance explained</title><p id="P40">Assuming a multiplicative model (within and between variants), the contribution to the sibling relative risk of a set of <italic>N</italic> SNPs is given by
<disp-formula id="FD1"><mml:math id="M1" display="block" overflow="scroll"><mml:mrow><mml:msub><mml:mi>λ</mml:mi><mml:mi>s</mml:mi></mml:msub><mml:mo>=</mml:mo><mml:mstyle displaystyle="true"><mml:munderover><mml:mo>∏</mml:mo><mml:mrow><mml:mi>j</mml:mi><mml:mo>=</mml:mo><mml:mn>1</mml:mn></mml:mrow><mml:mi>N</mml:mi></mml:munderover><mml:mrow><mml:msup><mml:mrow><mml:mrow><mml:mo>[</mml:mo><mml:mrow><mml:mn>1</mml:mn><mml:mo>+</mml:mo><mml:mfrac><mml:mrow><mml:msub><mml:mi>p</mml:mi><mml:mi>j</mml:mi></mml:msub><mml:mo stretchy="false">(</mml:mo><mml:mn>1</mml:mn><mml:mo>−</mml:mo><mml:msub><mml:mi>p</mml:mi><mml:mi>j</mml:mi></mml:msub><mml:mo stretchy="false">)</mml:mo><mml:msup><mml:mrow><mml:mrow><mml:mo>(</mml:mo><mml:mrow><mml:msub><mml:mi>ψ</mml:mi><mml:mi>j</mml:mi></mml:msub><mml:mo>−</mml:mo><mml:mn>1</mml:mn></mml:mrow><mml:mo>)</mml:mo></mml:mrow></mml:mrow><mml:mn>2</mml:mn></mml:msup></mml:mrow><mml:mrow><mml:mn>2</mml:mn><mml:msup><mml:mrow><mml:mrow><mml:mo>[</mml:mo><mml:mrow><mml:mo stretchy="false">(</mml:mo><mml:mn>1</mml:mn><mml:mo>−</mml:mo><mml:msub><mml:mi>p</mml:mi><mml:mi>j</mml:mi></mml:msub><mml:mo stretchy="false">)</mml:mo><mml:mo>+</mml:mo><mml:msub><mml:mi>p</mml:mi><mml:mi>j</mml:mi></mml:msub><mml:msub><mml:mi>ψ</mml:mi><mml:mi>j</mml:mi></mml:msub></mml:mrow><mml:mo>]</mml:mo></mml:mrow></mml:mrow><mml:mn>2</mml:mn></mml:msup></mml:mrow></mml:mfrac></mml:mrow><mml:mo>]</mml:mo></mml:mrow></mml:mrow><mml:mn>2</mml:mn></mml:msup></mml:mrow></mml:mstyle></mml:mrow></mml:math></disp-formula>where <italic>p<sub>j</sub></italic> and <italic>ψ<sub>j</sub></italic> denote the RAF and corresponding allelic OR at the <italic>j</italic>th SNP<sup><xref rid="R52" ref-type="bibr">52</xref></sup>. Assuming disease prevalence, <italic>K</italic>, the liability-scale variance<sup><xref rid="R20" ref-type="bibr">20</xref></sup> explained by these SNPs is given by
<disp-formula id="FD2"><mml:math id="M2" display="block" overflow="scroll"><mml:mrow><mml:msubsup><mml:mi>h</mml:mi><mml:mi>L</mml:mi><mml:mn>2</mml:mn></mml:msubsup><mml:mo>=</mml:mo><mml:mfrac><mml:mrow><mml:mn>2</mml:mn><mml:mrow><mml:mo>[</mml:mo><mml:mrow><mml:mi>T</mml:mi><mml:mo>−</mml:mo><mml:msub><mml:mi>T</mml:mi><mml:mn>1</mml:mn></mml:msub><mml:msqrt><mml:mrow><mml:mrow><mml:mo>(</mml:mo><mml:mrow><mml:mn>1</mml:mn><mml:mo>−</mml:mo><mml:mo stretchy="false">(</mml:mo><mml:msup><mml:mi>T</mml:mi><mml:mn>2</mml:mn></mml:msup><mml:mo>−</mml:mo><mml:msubsup><mml:mi>T</mml:mi><mml:mn>1</mml:mn><mml:mn>2</mml:mn></mml:msubsup><mml:mo stretchy="false">)</mml:mo><mml:mo stretchy="false">(</mml:mo><mml:mn>1</mml:mn><mml:mo>−</mml:mo><mml:mi>T</mml:mi><mml:mo>/</mml:mo><mml:mi>ω</mml:mi><mml:mo stretchy="false">)</mml:mo></mml:mrow><mml:mo>]</mml:mo></mml:mrow></mml:mrow></mml:msqrt></mml:mrow><mml:mo>)</mml:mo></mml:mrow></mml:mrow><mml:mrow><mml:mi>ω</mml:mi><mml:mo>+</mml:mo><mml:msubsup><mml:mi>T</mml:mi><mml:mn>1</mml:mn><mml:mn>2</mml:mn></mml:msubsup><mml:mo stretchy="false">(</mml:mo><mml:mi>ω</mml:mi><mml:mo>−</mml:mo><mml:mi>T</mml:mi><mml:mo stretchy="false">)</mml:mo></mml:mrow></mml:mfrac></mml:mrow></mml:math></disp-formula>In this expression, <italic>T</italic>=φ<sup>−1</sup>(1-<italic>K</italic>), <italic>T</italic><sub>1</sub>=φ<sup>−1</sup>(1-λ<sub>S</sub><italic>K</italic>), and <italic>ω</italic>=<italic>z</italic>/<italic>K</italic>, where <italic>z</italic> is the height of the standard Gaussian density at <italic>T</italic>.</p></sec><sec id="S18"><title>Z-score mixture modelling</title><p id="P41">We considered the distribution of <italic>Z</italic>-scores from the Stage 2 meta-analysis, aligned to the risk allele from Stage 1, at a subset of 3,412 independent T2D replication variants (CEU <italic>r</italic><sup>2</sup> < 0.05), excluding lead SNPs and proxies (CEU <italic>r</italic><sup>2</sup> ≥ 0.1) at the 63 established and newly discovered susceptibility loci on Metabochip. The Stage 2 <italic>Z</italic>-scores were modelled as a mixture of two Gaussian distributions: (i) with mean zero and unit variance (i.e. under the null hypothesis of no association); and (ii) with unknown mean (greater than zero) and variance (i.e. under the alternative hypothesis). The mean and variance of the alternative distribution, and the mixing proportion, were estimated using an expectation-maximization algorithm.</p><p id="P42">We estimated the posterior probability that each of the 3,412 independent replication SNPs is truly associated with T2D from the mixture distribution. We approximated the contribution of these SNPs to λ<sub>S</sub> by simulation from the mixture distribution. For each simulated replicate, we selected “causal” variants at random from these SNPs according to their posterior probability of association. Over 1,000 replicates, we approximated the mean and 95% CI for: (i) the number of “causal” variants among the 3,412 independent replication SNPs; and (ii) the contribution to λ<sub>S</sub>, using estimated RAFs and allelic ORs from the Stage 2 meta-analysis. For each replicate, we also generated a hypothetical third stage to the study consisting of 100,000 T2D cases and 100,000 controls. For each “causal” variant, we generated association summary statistics (<italic>Z</italic>-score aligned to the risk allele from Stage 1) according to the RAF and allelic OR from our Stage 2 meta-analysis.</p></sec><sec id="S19"><title>Assessment of allele frequency variation across European populations</title><p id="P43">We calculated F-statistics (<italic>F<sub>ST</sub></italic>) across European populations using data from the 1000 Genomes Project (CEU, TSI, FIN, GBR and IBS)<sup><xref rid="R13" ref-type="bibr">13</xref></sup> for the subset of SNPs selected for replication on Metabochip. <italic>F<sub>ST</sub></italic> was calculated by comparing mean heterozygosity across all populations to the mean within each sub-population, weighted by the number of contributing chromosomes from each sub-population. We compared <italic>F<sub>ST</sub></italic> for the subset of T2D replication SNPs that were directionally consistent between Stage 1 and Stage 2 meta-analyses with all Metabochip replication SNPs (up to 65,345 SNPs), using the Kolmogorov-Smirnov test.</p></sec><sec id="S20"><title>False-discovery rate (FDR) analysis</title><p id="P44">We undertook FDR analysis<sup><xref rid="R53" ref-type="bibr">53</xref></sup> of 64,646 Metabochip replication SNPs using combined meta-analysis <italic>P</italic>-values. From this analysis, we observed π̂<sub>0</sub> = 0.88, consistent with an excess of true positives in this set. We compared these <italic>P</italic>-values with FDR <italic>Q</italic>-values and posterior probabilities of membership to the alternative distribution from the mixture model (<xref ref-type="supplementary-material" rid="SD2">Supplementary Fig. 4</xref>) at the set of 2,172 T2D replication SNPs with concordant direct of allelic effect in both stages of the meta-analysis, after exclusion of 11 AT/GC SNPs with obvious strand orientation misalignments. FDR analysis also indicated an excess of expected true positives in this set of SNPs, even at relatively consistent thresholds (for example, we expect one false positive and 66 true positives at a <italic>Q</italic>-value of 0.014).</p></sec><sec id="S21"><title>Sex-differentiated meta-analysis</title><p id="P45">The Stage 1, Stage 2 and combined meta-analyses described above were repeated for males and females separately with correction for population structure within each sex (<xref ref-type="supplementary-material" rid="SD2">Supplementary Fig. 13</xref>). The male-specific meta-analysis consisted of 20,219 cases and 54,604 controls, while the female-specific meta-analysis consisted of 14,621 cases and 60,377 controls. The sex-specific meta-analyses were then combined to conduct a sex-differentiated test of association and a test of heterogeneity in allelic effects between males and females<sup><xref rid="R32" ref-type="bibr">32</xref></sup>.</p></sec><sec id="S22"><title>Physiological analyses</title><p id="P46">We obtained summary statistics (association <italic>P</italic>-values and <italic>Z</italic>-scores for direction of effect or allelic effects and standard errors) for lead T2D SNPs in GWAS meta-analyses of metabolic traits in European descent populations. Summary statistics were aligned to the T2D risk allele from the combined meta-analysis. We obtained summary statistics for lead SNPs in all newly discovered and established loci for glycemic traits in non-diabetic individuals from the MAGIC Investigators<sup><xref rid="R5" ref-type="bibr">5</xref>, <xref rid="R34" ref-type="bibr">34</xref></sup>. For fasting glucose and fasting insulin, the meta-analysis comprised up to 133,010 individuals, genotyped with GWAS arrays and imputed on up to <sup>~</sup>2.5 million SNPs, or genotyped with Metabochip. We also considered surrogate estimates of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) derived by homeostasis model assessment in up to 38,238 individuals (from GWAS meta-analysis only since these traits were not investigated in the enlarged MAGIC Metabochip study). We obtained summary statistics for lead SNPs in the newly discovered T2D loci (also including <italic>GRB14</italic> and <italic>HMG20A</italic>) for BMI in up to 119,600 individuals from the GIANT Consortium<sup><xref rid="R15" ref-type="bibr">15</xref></sup>. To eliminate potential bias in BMI allelic effect estimates at T2D susceptibility loci<sup><xref rid="R54" ref-type="bibr">54</xref></sup>, we restricted our attention to meta-analysis of population-based studies not ascertained for disease status for <sup>~</sup>2.8 million directly genotyped and/or imputed SNPs. We obtained summary statistics for the same SNPs for plasma lipid concentrations from the Global Lipids Genetics Consortium<sup><xref rid="R16" ref-type="bibr">16</xref></sup>. This meta-analysis comprised <sup>~</sup>2.6 million directly genotyped and/or imputed SNPs assessed for association to plasma concentrations of: total cholesterol (up to 100,184 individuals); LDL (up to 95,454 individuals); HDL (up to 99,900 individuals); and triglycerides (up to 96,598 individuals).</p><p id="P47">We also examined T2D association summary statistics at lead SNPs for 37 established T1D susceptibility loci. For each of these SNPs, we reported the allelic OR (aligned to the T2D risk-allele) and <italic>P</italic>-values in: (i) our Stage 1 T2D meta-analysis; and (ii) a GWAS meta-analysis of 7,514 T1D cases and 9,045 population controls from European descent populations from the Type 1 Diabetes Genetics Consortium<sup><xref rid="R35" ref-type="bibr">35</xref></sup>.</p></sec><sec id="S23"><title>Expression analyses</title><p id="P48">We identified proxies (CEU <italic>r</italic><sup>2</sup> > 0.8) for each lead T2D SNP in our newly discovered loci (also including <italic>GRB14</italic> and <italic>HMG20A</italic>). We interrogated public databases and unpublished resources for <italic>cis</italic>-eQTL expression with these SNPs in multiple tissues (details of these resources are summarized in the <xref ref-type="supplementary-material" rid="SD2">Supplementary Note</xref>). The collated results from these resources met study-specific criteria for statistical significance for association with transcript expression. For each transcript associated with a lead T2D SNP (or proxy), we identified the lead <italic>cis</italic>-eQTL SNP, and then estimated LD between them using 1000 Genomes Project data to assess coincidence of the signals.</p><p id="P49">We subsequently tested for association of each lead T2D SNP with the expression of flanking transcripts (within a 1 Mb window) in 603 subcutaneous adipose tissue samples and 745 peripheral blood samples from individuals from the Icelandic population, genotyped using the Illumina HumanHap 300 Bead Array, and imputed up to <sup>~</sup>2.5M SNPs<sup><xref rid="R36" ref-type="bibr">36</xref></sup>. We modelled the log-average expression ratio of two fluorphores as a function of the allele count (expected allele count for imputed SNPs) in a linear regression framework, with adjustment for age and sex (and differential cell count for blood samples) as covariates. All <italic>P</italic>-values were also adjusted for the relatedness between individuals by simulating genotypes through the corresponding Icelandic genealogy<sup><xref rid="R55" ref-type="bibr">55</xref></sup>. We also identified the most strongly associated <italic>cis</italic>-eQTL SNP for each flanking transcript. We then performed a conditional test of association of the transcript with the <italic>cis</italic>-eQTL SNP within the same linear regression framework, with additional adjustment for the lead T2D SNP as a covariate. The conditional analyses determine whether the <italic>cis</italic>-eQTL SNP association with the transcript can be explained by the lead T2D SNP.</p><p id="P50">We searched the 1000 Genomes Project data (Phase I interim release) for non-synonymous variants in strong LD (CEU <italic>r</italic><sup>2</sup> > 0.8) with lead T2D SNPs in the newly discovered loci (also including <italic>GRB14</italic> and <italic>HMG20A</italic>). Identified non-synonymous variants were subsequently interrogated for likely downstream functional consequences using SIFT<sup><xref rid="R37" ref-type="bibr">37</xref></sup>.</p></sec><sec id="S24"><title>Pathway, text mining and PPI analyses</title><p id="P51">We generated two lists of transcripts on the basis of the results of the sex-combined and sex-differentiated meta-analyses. The “primary” list included: (i) the nearest transcript to the lead SNP at 41 previously reported common variant loci identified in European descent populations; (ii) the nearest transcript to the lead SNP at the ten newly identified loci (<italic>P</italic> < 5 × 10<sup>−8</sup>) from the sex-combined meta-analysis, including <italic>GRB14</italic> and <italic>HMG20A</italic>; (iii) the nearest transcript to the lead SNP at both novel signals (<italic>P</italic> < 5 × 10<sup>−8</sup>) from the sex-differentiated meta-analysis; (iv) the nearest transcript to the lead SNP at six additional loci with the strongest evidence of association (<italic>P</italic> < 5 × 10<sup>−7</sup>) from the sex-combined meta-analysis; and (v) 18 genes implicated in monogenic forms of diabetes<sup><xref rid="R38" ref-type="bibr">38</xref></sup>, not already overlapping other loci included in the list. The “secondary” list incorporated the nearest transcript to the lead SNP at 77 additional loci with posterior probability of association of at least 75% from the mixture model, not already included in the primary list.</p><p id="P52">We tested the hypothesis that a PPI network built from the 77 primary transcripts was significantly enriched for physical interaction over and above that expected by chance using DAPPLE<sup><xref rid="R41" ref-type="bibr">41</xref></sup>. To build networks, DAPPLE uses a refined database of high-confidence interactions<sup><xref rid="R39" ref-type="bibr">39</xref>, <xref rid="R40" ref-type="bibr">40</xref></sup>, which emphasizes confidence of interaction over completeness, with the result that not all proteins are represented. We considered two categories of interactions: direct (i.e. between the associated transcripts themselves) and indirect (i.e. via common interactors that were not among the associated transcripts). We assessed the significance of the enrichment of physical interactions by permutation. Subsequently, we used the network as a “seeds” to query against the 77 secondary transcripts.</p><p id="P53">We used GRAIL to highlight genes from T2D susceptibility loci using similarity of text in PubMed abstracts or in gene-ontology associated codes<sup><xref rid="R42" ref-type="bibr">42</xref></sup>. To reduce confounding by published T2D GWAS analyses, we restricted our analysis to abstracts published prior to December 2006. We first tested for enrichment of connectivity in the list of 77 primary transcripts (treating the 18 monogenic loci as a single locus to reduce confounding), and assessed significance via permutation<sup><xref rid="R4" ref-type="bibr">4</xref></sup>. These gene sets were then used as the “seed” against which the list of 77 secondary transcripts was queried for connectivity.</p><p id="P54">We employed a two-step GSEA strategy to test for enrichment of transcripts in T2D susceptibility loci within pathways pertaining to 16 biological hypotheses related to disease pathogenesis (full details of these hypotheses are presented in the <xref ref-type="supplementary-material" rid="SD2">Supplementary Note</xref>). In the first step, we applied MAGENTA<sup><xref rid="R46" ref-type="bibr">46</xref></sup> to the Stage 1 meta-analysis. Genes in each pathway were scored on the basis of the most significant “local” SNP association using −110 kb/+40 kb boundaries. The 95<sup>th</sup> percentile of association <italic>P</italic>-values from all genes in the genome was used to determine the enrichment cut-off. In the second “replication” step, nominally significant gene sets from step one (MAGENTA <italic>P</italic> < 0.05) were tested for enrichment of T2D association signals in the Stage 2 meta-analysis. To account for the bias in the Metabochip design to SNPs nominally associated with T2D and related metabolic traits, we employed a modified GSEA approach. We tested for enrichment among a broader set of primary or primary and secondary transcripts within LD regions defined by <italic>r</italic><sup>2</sup> > 0.5 on either side of the lead SNP, extended to the nearest recombination hotspot and then an additional 50 kb (if there was no gene within the LD region, we used the nearest transcript). For robustness testing, we also examined enrichment in the nearest gene to the lead SNPs. The modified GSEA <italic>P</italic>-value was computed as the fraction of randomly sampled sets of loci, matched for number and local gene density to our primary and secondary lists, which have the same or more significant hyper-geometric probability than that of the T2D loci. For the “null” set, we used 1,600 LD-pruned Metabochip T2D replication SNPs with the lowest posterior probability of association (<5%) from the mixture model. To control for potential confounders, we applied the modified GSEA approach to two negative control lists: (i) loci defined by the lowest ranked independent T2D replication SNPs from our Stage 2 meta-analysis; and (ii) loci for QT-interval on the basis of our Stage 2 meta-analysis for independent replication SNPs for this trait, excluding those within our primary and secondary lists of T2D susceptibility loci and those near monogenic diabetes genes.</p></sec></sec><sec sec-type="supplementary-material" id="SM"><title>Supplementary Material</title><supplementary-material content-type="local-data" id="SD1"><label>1</label><media xlink:href="NIHMS393294-supplement-1.xlsx" mimetype="application" mime-subtype="octet-stream" orientation="portrait" xlink:type="simple" id="d37e4607" position="anchor"></media></supplementary-material><supplementary-material content-type="local-data" id="SD2"><label>2</label><media xlink:href="NIHMS393294-supplement-2.pdf" mimetype="application" mime-subtype="pdf" orientation="portrait" xlink:type="simple" id="d37e4611" position="anchor"></media></supplementary-material></sec></body><back><ack id="S25"><title>ACKNOWLEDGMENTS</title><p id="P55">Funding for this study was provided by: Academy of Finland (77299, 102318, 110413, 118065, 123885, 124243, 129680, 129293, 129494, 136895, 139635, 141005, 213506, 251217); Agence Nationale de la Recherche (France); American Diabetes Association (7-08-MN-OK); Association Française des Diabétiques; Association de Langue Française pour l'Etude du Diabète et des Maladies Métaboliques (France); Association Diabète Risque Vasculaire (France); BDA Research (UK); British Heart Foundation (RG/98002; RG2008/08); Cancer Research UK; Central Norway Health Authority; Central Finland Hospital District; Center for Inherited Disease Research (CIDR) (USA) ; Chief Scientist Office, Scotland (CZB/4/672); City of Kuopio (Finland); City of Leutkirch (Germany); Dept of Health (UK); Deutsche Forschungsgemeinschaft (ER1 55/6-2); Diabetes UK; Doris Duke Charitable Foundation (USA); Estonian Government SF0180142s0; European Commission: ENGAGE (HEALTH-F4-2007- 201413); EXGENESIS (LSHM-CT-2004-005272); 245536; QLG1-CT-2002-00896; 2004310); European Commission (Marie Curie: FP7-PEOPLE-2010-IEF); European Regional Development Fund; Faculty of Medicine, Norwegian University of Science and Technology; Finnish Diabetes Association; Finnish Diabetes Research Foundation; Finnish Foundation for Cardiovascular Research; Finnish Heart Association; Finnish Medical Society; Folkhälsan Research Foundation (Finland); Food Standards Agency (UK); Foundation for Life and Health in Finland; Federal Ministry of Education and Research (BMBF) (Germany); Federal Ministry of Health (Germany); General Secretary of Research and Technology (Greece); German Center for Diabetes Research (DZD); German Research Council (GRK 1041); Great Wine Estates of the Margaret River region of Western Australia; Groupe d'Etude des Maladies Métaboliques et Systémiques (France); Harvard Medical School (USA); Heinz Nixdorf Foundation (Germany); Helmholtz Zentrum München-Research Center for Environment and Health (Germany); Helsinki University Central Hospital Research Foundation (Finland); IngaBritt and Arne Lundberg’s Research Foundation (Sweden) (grant nr. 359); Ministry of Health (Ricerca Corrente) (Italy); Karolinska Institutet (Sweden); Knut and Alice Wallenberg Foundation (Sweden) (KAW 2009.0243); Kuopio University Hospital (Finland); Municipal Heath Care Center and Hospital, Jakobstad, Finland; Ministry of Social Affairs and Health (Finland); Ministry of Education and Culture (Finland) (627;2004-2011); Ministry of Innovation, Science, Research and Technology of the state North Rhine-Westphalia (Germany); Medical Research Council (UK) (G0000649,G0601261); MRC-GSK pilot programme grant (UK); Munich Center of Health Sciences (MC Health) (Germany); National Genome Research Network (NGFN) (Germany); NHLBI (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, R01HL087641, R01HL59367, R01HL086694, N01-HC-25195, N02-HL-6-4278); NHGRI (U01HG004402, N01-HG-65403); National Institutes for Health (USA) (HHSN268200625226C, UL1RR025005, U01HG004399, 1R21NS064908, 1Z01-HG000024, AG028555, AG08724, AG04563, AG10175, AG08861, CA055075); NIDDK (DK062370, DK058845, DK072193, DK078616, DK080140, DK073490); Närpes Health Care Foundation (Finland); National Health Screening Service of Norway; National Institute of Health Research (UK); National Institute for Health and Welfare (Finland) ; Nord-Trøndelag County Council (Norway); Nordic Center of Excellence in Disease Genetics; Norwegian Institute of Public Health; Norwegian Research Council; Novo Nordisk Fonden (Denmark); Ollqvist Foundation (Sweden); Oxford NIHR Biomedical Research Centre (UK); Paavo Nurmi Foundation (Finland); Päivikki and Sakari Sohlberg Foundation (Finland); Perklén Foundation (Sweden); Pfizer; Pirkanmaa Hospital District (Finland); Programme National de Recherche sur le Diabète (France); Programme Hospitalier de Recherche Clinique (French Ministry of Health); Region of Nord Pas De Calais (Contrat de Projets État-Région) (France); Research into Ageing (UK); Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center; Royal Swedish Academy of Sciences; Sarstedt AG & Co. (Germany); Signe and Ane Gyllenberg Foundation (Sweden); Slottery Machine Association (Finland); Social Insurance Institution of Finland (4/26/2010); South OstroBothnia Hospital District (Finland); State of Baden-Württemberg, Germany; Stockholm County Council (560183, 562183; Stroke Association (UK); Swedish Research Council (8691;09533; 2009-1039; Dnr 521-2010-3490, Dnr 521-2007-4037, Dnr 521-2008-2974, Dnr 825-2010-5983; Dnr 349-2008-6589); Swedish Cultural Foundation in Finland; Swedish Diabetes Foundation; Swedish Heart-Lung Foundation; Swedish Foundation for Strategic Research; Swedish Society of Medicine; Swedish Research Council; Swedish Research Council for Infrastructures; The Sigrid Juselius Foundation (Finland); Torsten and Ragnar Söderberg Foundation (Sweden) (MT33/09); University Hospital Essen (Germany); University of Tromsø (Norway); Uppsala University (Sweden); Uppsala University Hospital (Sweden); Wellcome Trust (GR072960; 076113, 077016, 081682, 083948, 083270, 084711, 086596, 090367, 090532, 098051). A more detailed set of acknowledgements is provided in the <xref ref-type="supplementary-material" rid="SD2">Supplementary Note</xref>.</p></ack><fn-group><fn id="FN5" fn-type="con"><p id="P56"><bold>AUTHOR CONTRIBUTIONS</bold></p><p id="P57"><bold>Writing group:</bold> A.P.M., B.F.V., T.M.T., T. Ferreira, A.V.S., V. Steinthorsdottir, R.J.S., H.K., H.G., A. Mahajan, I.P., M.B., M.I.M.</p><p id="P58"><bold>GWAS re-analysis:</bold> A.P.M., B.F.V., A.V.S., V. Steinthorsdottir, H.G., I.P., C.D., C.M.L., N.W.R., L.J.S., S.W., S. Raychaudhuri, H. Chen, C.F., C. Liu, D.R., D.J.C., W.H.L.K., M. Li, C.M.C., P.K., Q.S., R.M.v.D., H.M.S., P.S.C., A. Kong, N.R., G.T., R.B., L.L.B., N.B., G.C., C.J.G., C. Guiducci, C.H., W.R., N.K., C. Sigurðsson, B.T., H. Campbell, C.v.D., A.G.U., A. Hofman, E.S., G.R.A., K.R.O., E.Z., B.B., C.N.A.P., V. Lyssenko, T. Tuomi, B.I., D.J.H., L.Q., M.R., J.F.W., F.S.C., K.L.M., R.N.B., J. Tuomilehto, S.C., P. Froguel, T.I., A.D.M., T.M.F., A.T.H., E.B., P.M.N., U.T., L.C.G., K. Stefansson, F.H., J.S.P., J. Dupuis, J.B.M., D.A., M.B., M.I.M.</p><p id="P59"><bold>Metabochip design:</bold> B.F.V., H.M.K., G.R.A., D.A., M.B., M.I.M.</p><p id="P60"><bold>Metabochip samples:</bold> P.A., M.A., R.B., G.C., A.S.F.D., M.D., T. Forsen, B.G., C.H., A.B.H, A. James, A. Jonsson, W.R., J. Kravic, K.L., E.L., S. Männistö, B.M., L.R., J. Saramies, B.S., S. Shah, G. Sigurðsson G, A. Silveira, G. Steinbach, B.T., F.V., R.W., D.Z., M.D.T., N.G.F., J.G.E., B.B., C.N.A.P., V. Lyssenko, T.T., B.I., A.R.S., M.R., I.B., J.B., K. Hovingh, J.F.P., J.F.W., R.R., T.A.L., L.L., G.D., I.N., N.L.P., K. Khaw, N.J.W., S.M.K., T.E.S., T.W., E.K., J. Saltevo, M. Laakso, J. Kuusisto, A. Metspalu, F.S.C., K.L.M., R.N.B., J. Tuomilehto, B.O.B., C. Gieger, K. Hveem, S.C., P. Froguel, D.B., E. Tremoli, S.E. Humphries, D.S., J. Danesh, E.I., S. Ripatti, V. Salomaa, R.E., K.H.J., S. Moebus, A.P., T.I., U.dF., A. Hamsten, A.D.M., P.J.D., T.M.F., A.T.H., O.M., S. Kathiresan, P.M.N., P.D., U.T., L.C.G., K. Stefansson, D.A., M.B., M.I.M.</p><p id="P61"><bold>Metabochip genotyping:</bold> L.L.B., J.C., A.T.C., S.E., E.E., G.G.B, C.J.G., C. Guiducci, J.H., N.K., K. Krjutškov, C. Langford, S.L., G.M., T.W.M., M.P., J. Trakalo, W.W., A. Syvänen, L.P., M.M.N.</p><p id="P62"><bold>Metabochip analysis:</bold> A.P.M., B.F.V., T.M.T., T. Ferreira, A.V.S., V. Steinsthorsdottir, R.J.S., H.K., H.G., A. Mahajan, I.P., T.E., R.M.F., S. Kanoni, L.K., A. Kumar, V. Lagou, J.L., C.M.L., M.M., S. Pechlivanis, N.W.R., L.J.S., S.W., L.Y., H.M.S., P.S.C., K.F., P. Fontanillas, O.L.H., S.E. Hunt, A.U.J., A. Kong, R.L., J.M., J.R.B.P., C.G.P.P., S. Potter, E.R., N.R., S. Sivapalaratnam, S. Stančáková, K. Stirrups, G.T., E. Tikkanen, A.R.W., K.G.</p><p id="P63"><bold>Core and additional analyses:</bold> A.P.M., B.F.V., T.M.T., T. Ferreira, A.V.S., V. Steinsthorsdottir, R.J.S., H.K., H.G., A. Mahajan, I.P., E.J.R., S. Raychaudhuri, A.D.J., A.S.D., R.J.F.L., S.V., V.E., M.B., M.I.M.</p><p id="P64"><bold>Consortium management:</bold> A.P.M., B.F.V., T.M.T., H.G., C. Langenberg, J.C.F., H. Campbell, C.v.D., G.R.A., K.R.O., E.Z., C.N.A.P., V. Lyssenko, A.R.S., I.B., J.F.W., K.L.M., C. Gieger, S.C., P. Froguel, E.I., T.I., A.D.M., T.M.F., A.T.H., U.T., L.C.G., K. Stefansson, F.H., J.S.P., J.B.M., D.A., M.B., M.I.M.</p></fn><fn id="FN6"><p id="P65"><bold>COMPETING FINANCIAL INTERESTS</bold></p><p id="P66">Valgerdur Steinthorsdottir, Gudmar Thorleifsson, Unnur Thorsteinsdottir and Kari Stefansson are employees at deCODE genetics, a biotechnology company that provides genetic testing services, and own stock/stock options in the company. Jose Florez received consulting honoraria from Novartis, Lilly and Pfizer. Inês Barroso and spouse own stock in Glaxosmithkline and Incyte Ltd.</p></fn><fn id="FN7"><p id="P67"><bold>EdSumm (same for AOP and issue):</bold></p><p id="P68">Mark McCarthy, Michael Boehnke, Andrew Morris and colleagues perform large-scale association analyses using the Metabochip to gain insights into the genetic architecture of type 2 diabetes. 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The <italic>Z</italic>-score distribution is a mixture of: (i) the “null distribution” of SNPs having no effect on T2D (blue curve); and (ii) the “alternative distribution” of SNPs associated with the disease (red curve).</p></caption><graphic xlink:href="nihms393294f1"></graphic></fig><fig id="F2" orientation="portrait" position="float"><label>Figure 2</label><caption><p id="P70">Regional plots of T2D susceptibility loci with evidence of multiple association signals. Each point represents a Metabochip SNP passing quality control in our combined meta-analysis, plotted with their <italic>P</italic>-value (on a -log<sub>10</sub> scale) as a function of genomic position (NCBI Build 36). In each panel, the lead SNP is represented by the purple diamond. The color coding of all other SNPs (circles) indicates LD with the lead SNP (estimated by CEU <italic>r</italic><sup>2</sup> from the 1000 Genomes Project June 2010 release): red <italic>r</italic><sup>2</sup> ≥ 0.8; gold 0.6 ≤ <italic>r</italic><sup>2</sup> < 0.8; green 0.4 ≤ <italic>r</italic><sup>2</sup> < 0.6; cyan 0.2 ≤ <italic>r</italic><sup>2</sup> < 0.4; blue <italic>r</italic><sup>2</sup> < 0.2; grey <italic>r</italic><sup>2</sup> unknown. Recombination rates are estimated from the International HapMap Project and gene annotations are taken from the University of California Santa Cruz genome browser.</p></caption><graphic xlink:href="nihms393294f2"></graphic></fig><fig id="F3" orientation="portrait" position="float"><label>Figure 3</label><caption><p id="P71">Functional analyses. (<bold>a,b</bold>) Protein-protein interaction (PPI) sub-network for CREBBP and adipocytokine interactions. All direct interactions and common interactors between direct connections were extracted from the larger network of 314 proteins defined in the DAPPLE network analysis. Genes in the network are circles (nodes), colored according to the statistical relationship with T2D: common interactors between GWAS identified or monogenic loci are depicted as grey, monogenic loci (only) in blue, GWAS identified loci (only) in red, and loci with GWAS association and implicated by monogenic forms of diabetes are shown in green. Each interaction defined in the inWEB network is depicted by a line (edge) between nodes. (<bold>c</bold>) GRAIL circle plot of locus connectivity. Each locus is plotted in a circle where significant connections (<italic>P</italic> < 0.05) based on PubMed abstracts are drawn spanning the circle. Conservatively, we treated all monogenic loci (region 142) as a single locus by which connectivity is assessed. The strongest connections (<italic>P</italic> < 0.001) are colored in bright red. (<bold>d</bold>) GSEA of associations in the adipocytokine signaling pathway. The black bars represent the Stage 1 meta-analysis <italic>P</italic>-values of 63 autosomal genes in the Adipocytokine Signaling pathways (KEGG). A density plot of the black bars is depicted in the top panel (red line). The replicating genes in the leading edge of the GSEA are listed. The Stage 2 modified GSEA <italic>P</italic> = 1.6×10<sup>−4</sup> was calculated based on both the primary and secondary transcripts using the LD locus definition.</p></caption><graphic xlink:href="nihms393294f3"></graphic></fig><table-wrap id="T1" position="float" orientation="landscape"><label>Table 1</label><caption><p id="P72">T2D susceptibility loci achieving genome-wide significance (combined meta-analysis <italic>P</italic> < 5×10<sup>−8</sup>) for the first time in European descent populations</p></caption><table frame="box" rules="all"><thead><tr><th align="left" rowspan="2" valign="middle" colspan="1">SNP</th><th align="center" rowspan="2" valign="middle" colspan="1">Chr</th><th align="center" rowspan="2" valign="middle" colspan="1">Position<break></break>(Build 36)</th><th align="center" colspan="2" rowspan="1">Alleles<xref ref-type="table-fn" rid="TFN2">a</xref></th><th align="center" rowspan="2" valign="middle" colspan="1">Risk allele<break></break>frequency<xref ref-type="table-fn" rid="TFN3">b</xref></th><th align="center" rowspan="2" valign="middle" colspan="1">Nearby gene</th><th align="center" colspan="2" rowspan="1">Stage 1 meta-analysis: up to<break></break>12,171 cases and 56,862<break></break>controls</th><th align="center" colspan="2" rowspan="1">Stage 2 meta-analysis: up to<break></break>22,669 cases and 58,119<break></break>controls</th><th align="center" colspan="2" rowspan="1">Combined meta-analysis: up to<break></break>34,840 cases and 114,981 controls</th></tr><tr><th align="center" rowspan="1" colspan="1">Risk</th><th align="center" rowspan="1" colspan="1">Other</th><th align="center" rowspan="1" colspan="1">OR (95% CI)</th><th align="center" rowspan="1" colspan="1"><italic>P</italic>-value</th><th align="center" rowspan="1" colspan="1">OR (95% CI)</th><th align="center" rowspan="1" colspan="1"><italic>P</italic>-value</th><th align="center" rowspan="1" colspan="1">OR (95% CI)</th><th align="center" rowspan="1" colspan="1"><italic>P</italic>-value</th></tr></thead><tbody><tr><td align="left" colspan="13" rowspan="1"><bold>New loci not previously reported in any population</bold></td></tr><tr><td align="left" rowspan="1" colspan="1">rs12571751</td><td align="center" rowspan="1" colspan="1">10</td><td align="center" rowspan="1" colspan="1">80,612,637</td><td align="center" rowspan="1" colspan="1">A</td><td align="center" rowspan="1" colspan="1">G</td><td align="center" rowspan="1" colspan="1">0.52</td><td align="center" rowspan="1" colspan="1"><italic>ZMIZ1</italic></td><td align="center" rowspan="1" colspan="1">1.09 (1.06–1.13)</td><td align="center" rowspan="1" colspan="1">7.0×10<sup>−7</sup></td><td align="center" rowspan="1" colspan="1">1.07 (1.04–1.10)</td><td align="center" rowspan="1" colspan="1">1.5×10<sup>−6</sup></td><td align="center" rowspan="1" colspan="1">1.08 (1.05–1.10)</td><td align="center" rowspan="1" colspan="1">1.0×10<sup>−10</sup></td></tr><tr><td align="left" rowspan="1" colspan="1">rs516946</td><td align="center" rowspan="1" colspan="1">8</td><td align="center" rowspan="1" colspan="1">41,638,405</td><td align="center" rowspan="1" colspan="1">C</td><td align="center" rowspan="1" colspan="1">T</td><td align="center" rowspan="1" colspan="1">0.76</td><td align="center" rowspan="1" colspan="1"><italic>ANK1</italic></td><td align="center" rowspan="1" colspan="1">1.10 (1.06–1.15)</td><td align="center" rowspan="1" colspan="1">2.1×10<sup>−6</sup></td><td align="center" rowspan="1" colspan="1">1.08 (1.05–1.12)</td><td align="center" rowspan="1" colspan="1">1.1×10<sup>−6</sup></td><td align="center" rowspan="1" colspan="1">1.09 (1.06–1.12)</td><td align="center" rowspan="1" colspan="1">2.5×10<sup>−10</sup></td></tr><tr><td align="left" rowspan="1" colspan="1">rs10842994</td><td align="center" rowspan="1" colspan="1">12</td><td align="center" rowspan="1" colspan="1">27,856,417</td><td align="center" rowspan="1" colspan="1">C</td><td align="center" rowspan="1" colspan="1">T</td><td align="center" rowspan="1" colspan="1">0.80</td><td align="center" rowspan="1" colspan="1"><italic>KLHDC5</italic></td><td align="center" rowspan="1" colspan="1">1.09 (1.04–1.13)</td><td align="center" rowspan="1" colspan="1">3.0×10<sup>−4</sup></td><td align="center" rowspan="1" colspan="1">1.10 (1.07–1.14)</td><td align="center" rowspan="1" colspan="1">2.8×10<sup>−8</sup></td><td align="center" rowspan="1" colspan="1">1.10 (1.06–1.13)</td><td align="center" rowspan="1" colspan="1">6.1×10<sup>−10</sup></td></tr><tr><td align="left" rowspan="1" colspan="1">rs2796441</td><td align="center" rowspan="1" colspan="1">9</td><td align="center" rowspan="1" colspan="1">83,498,768</td><td align="center" rowspan="1" colspan="1">G</td><td align="center" rowspan="1" colspan="1">A</td><td align="center" rowspan="1" colspan="1">0.57</td><td align="center" rowspan="1" colspan="1"><italic>TLE1</italic></td><td align="center" rowspan="1" colspan="1">1.07 (1.03–1.12)</td><td align="center" rowspan="1" colspan="1">4.8×10<sup>−4</sup></td><td align="center" rowspan="1" colspan="1">1.07 (1.04–1.10)</td><td align="center" rowspan="1" colspan="1">3.3×10<sup>−7</sup></td><td align="center" rowspan="1" colspan="1">1.07 (1.05–1.10)</td><td align="center" rowspan="1" colspan="1">5.4×10<sup>−9</sup></td></tr><tr><td align="left" rowspan="1" colspan="1">rs459193</td><td align="center" rowspan="1" colspan="1">5</td><td align="center" rowspan="1" colspan="1">55,842,508</td><td align="center" rowspan="1" colspan="1">G</td><td align="center" rowspan="1" colspan="1">A</td><td align="center" rowspan="1" colspan="1">0.70</td><td align="center" rowspan="1" colspan="1"><italic>ANKRD55</italic></td><td align="center" rowspan="1" colspan="1">1.05 (1.01–1.10)</td><td align="center" rowspan="1" colspan="1">2.7×10<sup>−2</sup></td><td align="center" rowspan="1" colspan="1">1.10 (1.06–1.13)</td><td align="center" rowspan="1" colspan="1">2.0×10<sup>−9</sup></td><td align="center" rowspan="1" colspan="1">1.08 (1.05–1.11)</td><td align="center" rowspan="1" colspan="1">6.0×10<sup>−9</sup></td></tr><tr><td align="left" rowspan="1" colspan="1">rs10401969</td><td align="center" rowspan="1" colspan="1">19</td><td align="center" rowspan="1" colspan="1">19,268,718</td><td align="center" rowspan="1" colspan="1">C</td><td align="center" rowspan="1" colspan="1">T</td><td align="center" rowspan="1" colspan="1">0.08</td><td align="center" rowspan="1" colspan="1"><italic>CILP2</italic></td><td align="center" rowspan="1" colspan="1">1.13 (1.05–1.21)</td><td align="center" rowspan="1" colspan="1">9.2×10<sup>−4</sup></td><td align="center" rowspan="1" colspan="1">1.14 (1.08–1.20)</td><td align="center" rowspan="1" colspan="1">2.0×10<sup>−7</sup></td><td align="center" rowspan="1" colspan="1">1.13 (1.09–1.18)</td><td align="center" rowspan="1" colspan="1">7.0×10<sup>−9</sup></td></tr><tr><td align="left" rowspan="1" colspan="1">rs12970134</td><td align="center" rowspan="1" colspan="1">18</td><td align="center" rowspan="1" colspan="1">56,035,730</td><td align="center" rowspan="1" colspan="1">A</td><td align="center" rowspan="1" colspan="1">G</td><td align="center" rowspan="1" colspan="1">0.27</td><td align="center" rowspan="1" colspan="1"><italic>MC4R</italic></td><td align="center" rowspan="1" colspan="1">1.08 (1.03–1.12)</td><td align="center" rowspan="1" colspan="1">2.3×10<sup>−4</sup></td><td align="center" rowspan="1" colspan="1">1.08 (1.05–1.11)</td><td align="center" rowspan="1" colspan="1">2.0×10<sup>−6</sup></td><td align="center" rowspan="1" colspan="1">1.08 (1.05–1.11)</td><td align="center" rowspan="1" colspan="1">1.2×10<sup>−8</sup></td></tr><tr><td align="left" rowspan="1" colspan="1">rs7202877</td><td align="center" rowspan="1" colspan="1">16</td><td align="center" rowspan="1" colspan="1">73,804,746</td><td align="center" rowspan="1" colspan="1">T</td><td align="center" rowspan="1" colspan="1">G</td><td align="center" rowspan="1" colspan="1">0.89</td><td align="center" rowspan="1" colspan="1"><italic>BCAR1</italic></td><td align="center" rowspan="1" colspan="1">1.15 (1.07–1.23)</td><td align="center" rowspan="1" colspan="1">5.0×10<sup>−5</sup></td><td align="center" rowspan="1" colspan="1">1.10 (1.05–1.15)</td><td align="center" rowspan="1" colspan="1">1.9×10<sup>−5</sup></td><td align="center" rowspan="1" colspan="1">1.12 (1.07–1.16)</td><td align="center" rowspan="1" colspan="1">3.5×10<sup>−8</sup></td></tr><tr><td align="left" colspan="13" rowspan="1"><bold>Loci not previously reported in European descent populations</bold></td></tr><tr><td align="left" rowspan="1" colspan="1">rs7177055</td><td align="center" rowspan="1" colspan="1">15</td><td align="center" rowspan="1" colspan="1">75,619,817</td><td align="center" rowspan="1" colspan="1">A</td><td align="center" rowspan="1" colspan="1">G</td><td align="center" rowspan="1" colspan="1">0.68</td><td align="center" rowspan="1" colspan="1"><italic>HMG20A</italic></td><td align="center" rowspan="1" colspan="1">1.08 (1.04–1.12)</td><td align="center" rowspan="1" colspan="1">1.2×10<sup>−4</sup></td><td align="center" rowspan="1" colspan="1">1.08 (1.05–1.11)</td><td align="center" rowspan="1" colspan="1">8.8×10<sup>−7</sup></td><td align="center" rowspan="1" colspan="1">1.08 (1.05–1.10)</td><td align="center" rowspan="1" colspan="1">4.6×10<sup>−9</sup></td></tr><tr><td align="left" rowspan="1" colspan="1">rs13389219</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">165,237,122</td><td align="center" rowspan="1" colspan="1">C</td><td align="center" rowspan="1" colspan="1">T</td><td align="center" rowspan="1" colspan="1">0.60</td><td align="center" rowspan="1" colspan="1"><italic>GRB14</italic></td><td align="center" rowspan="1" colspan="1">1.05 (1.01–1.09)</td><td align="center" rowspan="1" colspan="1">1.3×10<sup>−2</sup></td><td align="center" rowspan="1" colspan="1">1.09 (1.06–1.12)</td><td align="center" rowspan="1" colspan="1">9.5×10<sup>−9</sup></td><td align="center" rowspan="1" colspan="1">1.07 (1.05–1.10)</td><td align="center" rowspan="1" colspan="1">1.0×10<sup>−8</sup></td></tr></tbody></table><table-wrap-foot><fn id="TFN1"><p id="P73">Chr, chromosome; OR, odds ratio; CI, confidence interval.</p></fn><fn id="TFN2"><label>a</label><p id="P74">Alleles are aligned to the forward strand of NCBI Build 36.</p></fn><fn id="TFN3"><label>b</label><p id="P75">Weighted mean frequency of T2D risk allele across Stage 2 studies.</p></fn></table-wrap-foot></table-wrap><table-wrap id="T2" position="float" orientation="landscape"><label>Table 2</label><caption><p id="P76">T2D susceptibility loci with sex-differentiated evidence of association</p></caption><table frame="box" rules="all"><thead><tr><th align="left" rowspan="2" valign="middle" colspan="1">SNP</th><th align="center" rowspan="2" valign="middle" colspan="1">Chr</th><th align="center" rowspan="2" valign="middle" colspan="1">Position<break></break>(Build 36)</th><th align="center" colspan="2" rowspan="1">Alleles<xref ref-type="table-fn" rid="TFN5">a</xref></th><th align="center" rowspan="2" valign="middle" colspan="1">Risk allele<break></break>frequency<xref ref-type="table-fn" rid="TFN6">b</xref></th><th align="center" rowspan="2" valign="middle" colspan="1">Nearby gene</th><th align="center" colspan="2" rowspan="1">Male meta-analysis: up to<break></break>20,219 cases and 54,604 controls</th><th align="center" colspan="2" rowspan="1">Female meta-analysis: up to<break></break>14,621 cases and 60,377 controls</th><th align="center" colspan="2" rowspan="1">Sex-differentiated meta-analysis: up to<break></break>34,840 cases and 114,981 controls</th></tr><tr><th align="center" rowspan="1" colspan="1">Risk</th><th align="center" rowspan="1" colspan="1">Other</th><th align="center" rowspan="1" colspan="1">OR (95% CI)</th><th align="center" rowspan="1" colspan="1"><italic>P</italic>-value</th><th align="center" rowspan="1" colspan="1">OR (95% CI)</th><th align="center" rowspan="1" colspan="1"><italic>P</italic>-value</th><th align="center" rowspan="1" colspan="1">Association <italic>P</italic>-value</th><th align="center" rowspan="1" colspan="1">Heterogeneity <italic>P</italic>-value</th></tr></thead><tbody><tr><td align="left" colspan="13" rowspan="1"><bold>New loci identified through sex-differentiated meta-analysis achieving genome-wide significance (<italic>P</italic> < 5×10 <sup>−8</sup>)</bold></td></tr><tr><td align="left" rowspan="1" colspan="1">rs11063069</td><td align="center" rowspan="1" colspan="1">12</td><td align="center" rowspan="1" colspan="1">4,244,634</td><td align="center" rowspan="1" colspan="1">G</td><td align="center" rowspan="1" colspan="1">A</td><td align="center" rowspan="1" colspan="1">0.21</td><td align="center" rowspan="1" colspan="1"><italic>CCND2</italic></td><td align="center" rowspan="1" colspan="1">1.12 (1.08–1.16)</td><td align="center" rowspan="1" colspan="1">1.1×10<sup>−9</sup></td><td align="center" rowspan="1" colspan="1">1.04 (1.00–1.09)</td><td align="center" rowspan="1" colspan="1">3.6×10<sup>−2</sup></td><td align="center" rowspan="1" colspan="1">9.8×10<sup>−10</sup></td><td align="center" rowspan="1" colspan="1">1.3×10<sup>−2</sup></td></tr><tr><td align="left" rowspan="1" colspan="1">rs8108269</td><td align="center" rowspan="1" colspan="1">19</td><td align="center" rowspan="1" colspan="1">50,850,353</td><td align="center" rowspan="1" colspan="1">G</td><td align="center" rowspan="1" colspan="1">T</td><td align="center" rowspan="1" colspan="1">0.31</td><td align="center" rowspan="1" colspan="1"><italic>GIPR</italic></td><td align="center" rowspan="1" colspan="1">1.05 (1.02–1.08)</td><td align="center" rowspan="1" colspan="1">3.7×10<sup>−3</sup></td><td align="center" rowspan="1" colspan="1">1.10 (1.06–1.14)</td><td align="center" rowspan="1" colspan="1">2.2×10<sup>−7</sup></td><td align="center" rowspan="1" colspan="1">2.1×10<sup>−8</sup></td><td align="center" rowspan="1" colspan="1">5.7×10<sup>−2</sup></td></tr><tr><td align="left" colspan="13" rowspan="1"><bold>Other loci with nominally significant evidence (<italic>P</italic> < 0.05) of heterogeneity in allelic odds ratios between sexes</bold></td></tr><tr><td align="left" rowspan="1" colspan="1">rs163184</td><td align="center" rowspan="1" colspan="1">11</td><td align="center" rowspan="1" colspan="1">2,803,645</td><td align="center" rowspan="1" colspan="1">G</td><td align="center" rowspan="1" colspan="1">T</td><td align="center" rowspan="1" colspan="1">0.50</td><td align="center" rowspan="1" colspan="1"><italic>KCNQ1</italic></td><td align="center" rowspan="1" colspan="1">1.12 (1.09–1.16)</td><td align="center" rowspan="1" colspan="1">8.5×10<sup>−15</sup></td><td align="center" rowspan="1" colspan="1">1.05 (1.01–1.08)</td><td align="center" rowspan="1" colspan="1">7.8×10<sup>−3</sup></td><td align="center" rowspan="1" colspan="1">2.4×10<sup>−15</sup></td><td align="center" rowspan="1" colspan="1">1.3×10<sup>−3</sup></td></tr><tr><td align="left" rowspan="1" colspan="1">rs17168486</td><td align="center" rowspan="1" colspan="1">7</td><td align="center" rowspan="1" colspan="1">14,864,807</td><td align="center" rowspan="1" colspan="1">T</td><td align="center" rowspan="1" colspan="1">C</td><td align="center" rowspan="1" colspan="1">0.19</td><td align="center" rowspan="1" colspan="1"><italic>DGKB</italic></td><td align="center" rowspan="1" colspan="1">1.15 (1.11–1.19)</td><td align="center" rowspan="1" colspan="1">6.5×10<sup>−13</sup></td><td align="center" rowspan="1" colspan="1">1.06 (1.02–1.11)</td><td align="center" rowspan="1" colspan="1">5.2×10<sup>−3</sup></td><td align="center" rowspan="1" colspan="1">1.2×10<sup>−13</sup></td><td align="center" rowspan="1" colspan="1">6.8×10<sup>−3</sup></td></tr><tr><td align="left" rowspan="1" colspan="1">rs3923113</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">165,210,095</td><td align="center" rowspan="1" colspan="1">A</td><td align="center" rowspan="1" colspan="1">C</td><td align="center" rowspan="1" colspan="1">0.63</td><td align="center" rowspan="1" colspan="1"><italic>GRB14</italic></td><td align="center" rowspan="1" colspan="1">1.05 (1.01–1.08)</td><td align="center" rowspan="1" colspan="1">4.9×10<sup>−3</sup></td><td align="center" rowspan="1" colspan="1">1.11 (1.08–1.15)</td><td align="center" rowspan="1" colspan="1">1.8×10<sup>−9</sup></td><td align="center" rowspan="1" colspan="1">2.6×10<sup>−10</sup></td><td align="center" rowspan="1" colspan="1">8.0×10<sup>−3</sup></td></tr><tr><td align="left" rowspan="1" colspan="1">rs243088</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">60,422,249</td><td align="center" rowspan="1" colspan="1">T</td><td align="center" rowspan="1" colspan="1">A</td><td align="center" rowspan="1" colspan="1">0.45</td><td align="center" rowspan="1" colspan="1"><italic>BCL11A</italic></td><td align="center" rowspan="1" colspan="1">1.10 (1.06–1.13)</td><td align="center" rowspan="1" colspan="1">6.5×10<sup>−10</sup></td><td align="center" rowspan="1" colspan="1">1.04 (1.00–1.07)</td><td align="center" rowspan="1" colspan="1">2.8×10<sup>−2</sup></td><td align="center" rowspan="1" colspan="1">4.7×10<sup>−10</sup></td><td align="center" rowspan="1" colspan="1">1.2×10<sup>−2</sup></td></tr></tbody></table><table-wrap-foot><fn id="TFN4"><p id="P77">Chr, chromosome; OR, odds ratio; CI, confidence interval.</p></fn><fn id="TFN5"><label>a</label><p id="P78">Alleles are aligned to the forward strand of NCBI Build 36.</p></fn><fn id="TFN6"><label>b</label><p id="P79">Weighted mean frequency of T2D risk allele across Stage 2 studies.</p></fn></table-wrap-foot></table-wrap></floats-group></pmc></record>Pour manipuler ce document sous Unix 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