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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Genome-wide association and large scale follow-up identifies 16 new loci influencing lung function</title><author><name sortKey="Artigas, Maria Soler" sort="Artigas, Maria Soler" uniqKey="Artigas M" first="María Soler" last="Artigas">María Soler Artigas</name><affiliation><nlm:aff id="A1">Department of Health Sciences, University of Leicester, Leicester, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Genetics, University of Leicester, Leicester, UK</nlm:aff></affiliation></author><author><name sortKey="Loth, Daan W" sort="Loth, Daan W" uniqKey="Loth D" first="Daan W" last="Loth">Daan W. Loth</name><affiliation><nlm:aff id="A3">Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Inspectorate of Healthcare, The Hague, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Wain, Louise V" sort="Wain, Louise V" uniqKey="Wain L" first="Louise V" last="Wain">Louise V. Wain</name><affiliation><nlm:aff id="A1">Department of Health Sciences, University of Leicester, Leicester, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Genetics, University of Leicester, Leicester, UK</nlm:aff></affiliation></author><author><name sortKey="Gharib, Sina A" sort="Gharib, Sina A" uniqKey="Gharib S" first="Sina A" last="Gharib">Sina A. Gharib</name><affiliation><nlm:aff id="A5">Center for Lung Biology, University of Washington, Seattle, Washington, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A6">Department of Medicine, University of Washington, Seattle, Washington, USA</nlm:aff></affiliation></author><author><name sortKey="Obeidat, Ma N" sort="Obeidat, Ma N" uniqKey="Obeidat M" first="Ma N" last="Obeidat">Ma N Obeidat</name><affiliation><nlm:aff id="A7">Division of Therapeutics and Molecular Medicine, Nottingham Respiratory Biomedical Research Unit, University Hospital of Nottingham, Nottingham, London, UK</nlm:aff></affiliation></author><author><name sortKey="Tang, Wenbo" sort="Tang, Wenbo" uniqKey="Tang W" first="Wenbo" last="Tang">Wenbo Tang</name><affiliation><nlm:aff id="A8">Division of Nutritional Sciences, Cornell University Ithaca, New York, USA</nlm:aff></affiliation></author><author><name sortKey="Zhai, Guangju" sort="Zhai, Guangju" uniqKey="Zhai G" first="Guangju" last="Zhai">Guangju Zhai</name><affiliation><nlm:aff id="A9">Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A10">Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, Newfoundland, Canada</nlm:aff></affiliation></author><author><name sortKey="Zhao, Jing Hua" sort="Zhao, Jing Hua" uniqKey="Zhao J" first="Jing Hua" last="Zhao">Jing Hua Zhao</name><affiliation><nlm:aff id="A11">Medical Research Council (MRC) Epidemiology Unit, Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Smith, Albert Vernon" sort="Smith, Albert Vernon" uniqKey="Smith A" first="Albert Vernon" last="Smith">Albert Vernon Smith</name><affiliation><nlm:aff id="A12">Icelandic Heart Association, Kopavogur, Iceland</nlm:aff></affiliation><affiliation><nlm:aff id="A13">University of Iceland, Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Huffman, Jennifer E" sort="Huffman, Jennifer E" uniqKey="Huffman J" first="Jennifer E" last="Huffman">Jennifer E. Huffman</name><affiliation><nlm:aff id="A14">MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Albrecht, Eva" sort="Albrecht, Eva" uniqKey="Albrecht E" first="Eva" last="Albrecht">Eva Albrecht</name><affiliation><nlm:aff id="A15">Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany</nlm:aff></affiliation></author><author><name sortKey="Jackson, Catherine M" sort="Jackson, Catherine M" uniqKey="Jackson C" first="Catherine M" last="Jackson">Catherine M. Jackson</name><affiliation><nlm:aff id="A16">School of Medicine, University of St. Andrews, St. Andrews, Scotland, UK</nlm:aff></affiliation></author><author><name sortKey="Evans, David M" sort="Evans, David M" uniqKey="Evans D" first="David M" last="Evans">David M. Evans</name><affiliation><nlm:aff id="A17">MRC Centre for Causal Analyses in Translational Epidemiology, School of Social and Community Medicine, University of Bristol, Bristol, UK</nlm:aff></affiliation></author><author><name sortKey="Cadby, Gemma" sort="Cadby, Gemma" uniqKey="Cadby G" first="Gemma" last="Cadby">Gemma Cadby</name><affiliation><nlm:aff id="A18">Genetic Epidemiology and Biostatistics Platform, Ontario Institute for Cancer Research, Toronto, Ontario, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="A19">Prosserman Centre for Health Research, Samuel Lunenfeld Research Institute, Toronto, Ontario, Canada</nlm:aff></affiliation></author><author><name sortKey="Fornage, Myriam" sort="Fornage, Myriam" uniqKey="Fornage M" first="Myriam" last="Fornage">Myriam Fornage</name><affiliation><nlm:aff id="A20">Brown Foundation Institute of Molecular Medicine, University of Texas at Houston, Houston, Texas, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A21">Human Genetics Center, School of Public Health, University of Texas at Houston, Houston, Texas, USA</nlm:aff></affiliation></author><author><name sortKey="Manichaikul, Ani" sort="Manichaikul, Ani" uniqKey="Manichaikul A" first="Ani" last="Manichaikul">Ani Manichaikul</name><affiliation><nlm:aff id="A22">Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A23">Department of Public Health Sciences, Division of Biostatistics and Epidemiology, University of Virginia, Charlottesville, Virginia, USA</nlm:aff></affiliation></author><author><name sortKey="Lopez, Lorna M" sort="Lopez, Lorna M" uniqKey="Lopez L" first="Lorna M" last="Lopez">Lorna M. Lopez</name><affiliation><nlm:aff id="A24">Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A25">Department of Psychology, The University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Johnson, Toby" sort="Johnson, Toby" uniqKey="Johnson T" first="Toby" last="Johnson">Toby Johnson</name><affiliation><nlm:aff id="A26">Clinical Pharmacology and the Genome Centre, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Aldrich, Melinda C" sort="Aldrich, Melinda C" uniqKey="Aldrich M" first="Melinda C" last="Aldrich">Melinda C. Aldrich</name><affiliation><nlm:aff id="A27">Department of Thoracic Surgery, Vanderbilt University, Nashville, Tennessee, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A28">Division of Epidemiology, Vanderbilt University, Nashville, Tennessee, USA</nlm:aff></affiliation></author><author><name sortKey="Aspelund, Thor" sort="Aspelund, Thor" uniqKey="Aspelund T" first="Thor" last="Aspelund">Thor Aspelund</name><affiliation><nlm:aff id="A12">Icelandic Heart Association, Kopavogur, Iceland</nlm:aff></affiliation><affiliation><nlm:aff id="A13">University of Iceland, Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Barroso, Ines" sort="Barroso, Ines" uniqKey="Barroso I" first="Inês" last="Barroso">Inês Barroso</name><affiliation><nlm:aff id="A29">Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A30">University of Cambridge Metabolic Research Labs, Institute of Metabolic Science Addenbrooke’s Hospital, Cambridge, 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="A31">Centre for Population Health Sciences, The University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Cassano, Patricia A" sort="Cassano, Patricia A" uniqKey="Cassano P" first="Patricia A" last="Cassano">Patricia A. Cassano</name><affiliation><nlm:aff id="A8">Division of Nutritional Sciences, Cornell University Ithaca, New York, 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="A32">Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, USA</nlm:aff></affiliation></author><author><name sortKey="Eiriksdottir, Gudny" sort="Eiriksdottir, Gudny" uniqKey="Eiriksdottir G" first="Gudny" last="Eiriksdottir">Gudny Eiriksdottir</name><affiliation><nlm:aff id="A12">Icelandic Heart Association, Kopavogur, Iceland</nlm:aff></affiliation></author><author><name sortKey="Franceschini, Nora" sort="Franceschini, Nora" uniqKey="Franceschini N" first="Nora" last="Franceschini">Nora Franceschini</name><affiliation><nlm:aff id="A33">Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, USA</nlm:aff></affiliation></author><author><name sortKey="Garcia, Melissa" sort="Garcia, Melissa" uniqKey="Garcia M" first="Melissa" last="Garcia">Melissa Garcia</name><affiliation><nlm:aff id="A34">Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA</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="A15">Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany</nlm:aff></affiliation></author><author><name sortKey="Gislason, Gauti Kjartan" sort="Gislason, Gauti Kjartan" uniqKey="Gislason G" first="Gauti Kjartan" last="Gislason">Gauti Kjartan Gislason</name><affiliation><nlm:aff id="A12">Icelandic Heart Association, Kopavogur, Iceland</nlm:aff></affiliation></author><author><name sortKey="Grkovic, Ivica" sort="Grkovic, Ivica" uniqKey="Grkovic I" first="Ivica" last="Grkovic">Ivica Grkovic</name><affiliation><nlm:aff id="A35">Croatian Centre for Global Health, The University of Split Medical School, Split, Croatia</nlm:aff></affiliation></author><author><name sortKey="Hammond, Christopher J" sort="Hammond, Christopher J" uniqKey="Hammond C" first="Christopher J" last="Hammond">Christopher J. Hammond</name><affiliation><nlm:aff id="A9">Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Hancock, Dana B" sort="Hancock, Dana B" uniqKey="Hancock D" first="Dana B" last="Hancock">Dana B. Hancock</name><affiliation><nlm:aff id="A36">Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A37">Behavioral Health Epidemiology Program, Research Triangle Institute International, Research Triangle Park, North Carolina, USA</nlm:aff></affiliation></author><author><name sortKey="Harris, Tamara B" sort="Harris, Tamara B" uniqKey="Harris T" first="Tamara B" last="Harris">Tamara B. Harris</name><affiliation><nlm:aff id="A34">Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA</nlm:aff></affiliation></author><author><name sortKey="Ramasamy, Adaikalavan" sort="Ramasamy, Adaikalavan" uniqKey="Ramasamy A" first="Adaikalavan" last="Ramasamy">Adaikalavan Ramasamy</name><affiliation><nlm:aff id="A38"> Respiratory Epidemiology and Public Health, Imperial College London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A39">Department of Epidemiology and Biostatistics, Imperial College London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A40">Department of Medical and Molecular Genetics, King’s College London, Guy’s Hospital, London, UK</nlm:aff></affiliation></author><author><name sortKey="Heckbert, Susan R" sort="Heckbert, Susan R" uniqKey="Heckbert S" first="Susan R" last="Heckbert">Susan R. Heckbert</name><affiliation><nlm:aff id="A41">Cardiovascular Health Research Unit, University of Washington, Seattle, Washington, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A42">Department of Epidemiology, University of Washington, Seattle, Washington, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A43">Group Health Research Institute, Group Health Cooperative, Seattle, Washington, USA</nlm:aff></affiliation></author><author><name sortKey="Heliovaara, Markku" sort="Heliovaara, Markku" uniqKey="Heliovaara M" first="Markku" last="Heliövaara">Markku Heliövaara</name><affiliation><nlm:aff id="A44">National Institute for Health and Welfare, Helsinki, Finland</nlm:aff></affiliation></author><author><name sortKey="Homuth, Georg" sort="Homuth, Georg" uniqKey="Homuth G" first="Georg" last="Homuth">Georg Homuth</name><affiliation><nlm:aff id="A45">Interfaculty Institute for Genetics and Functional Genomics, Department of Functional Genomics, University of Greifswald, Greifswald, Germany</nlm:aff></affiliation></author><author><name sortKey="Hysi, Pirro G" sort="Hysi, Pirro G" uniqKey="Hysi P" first="Pirro G" last="Hysi">Pirro G. Hysi</name><affiliation><nlm:aff id="A9">Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK</nlm:aff></affiliation></author><author><name sortKey="James, Alan L" sort="James, Alan L" uniqKey="James A" first="Alan L" last="James">Alan L. James</name><affiliation><nlm:aff id="A46">Department of Pulmonary Physiology and Sleep Medicine/West Australian Sleep Disorders Research Institute, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A47">The School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A48">Busselton Population Medical Research Foundation, Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia</nlm:aff></affiliation></author><author><name sortKey="Jankovic, Stipan" sort="Jankovic, Stipan" uniqKey="Jankovic S" first="Stipan" last="Jankovic">Stipan Jankovic</name><affiliation><nlm:aff id="A35">Croatian Centre for Global Health, The University of Split Medical School, Split, Croatia</nlm:aff></affiliation></author><author><name sortKey="Joubert, Bonnie R" sort="Joubert, Bonnie R" uniqKey="Joubert B" first="Bonnie R" last="Joubert">Bonnie R. Joubert</name><affiliation><nlm:aff id="A36">Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA</nlm:aff></affiliation></author><author><name sortKey="Karrasch, Stefan" sort="Karrasch, Stefan" uniqKey="Karrasch S" first="Stefan" last="Karrasch">Stefan Karrasch</name><affiliation><nlm:aff id="A49">Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, Ludwig-Maximilians-University, Munich, 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="A50">Unit for Molecular Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany</nlm:aff></affiliation></author><author><name sortKey="Koch, Beate" sort="Koch, Beate" uniqKey="Koch B" first="Beate" last="Koch">Beate Koch</name><affiliation><nlm:aff id="A51">Department of Internal Medicine B, University Hospital Greifswald, Greifswald, Germany</nlm:aff></affiliation></author><author><name sortKey="Kritchevsky, Stephen B" sort="Kritchevsky, Stephen B" uniqKey="Kritchevsky S" first="Stephen B" last="Kritchevsky">Stephen B. Kritchevsky</name><affiliation><nlm:aff id="A52">Sticht Center on Aging, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA</nlm:aff></affiliation></author><author><name sortKey="Launer, Lenore J" sort="Launer, Lenore J" uniqKey="Launer L" first="Lenore J" last="Launer">Lenore J. Launer</name><affiliation><nlm:aff id="A34">Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA</nlm:aff></affiliation></author><author><name sortKey="Liu, Yongmei" sort="Liu, Yongmei" uniqKey="Liu Y" first="Yongmei" last="Liu">Yongmei Liu</name><affiliation><nlm:aff id="A53">Epidemiology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA</nlm:aff></affiliation></author><author><name sortKey="Loehr, Laura R" sort="Loehr, Laura R" uniqKey="Loehr L" first="Laura R" last="Loehr">Laura R. Loehr</name><affiliation><nlm:aff id="A33">Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, USA</nlm:aff></affiliation></author><author><name sortKey="Lohman, Kurt" sort="Lohman, Kurt" uniqKey="Lohman K" first="Kurt" last="Lohman">Kurt Lohman</name><affiliation><nlm:aff id="A54">Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA</nlm:aff></affiliation></author><author><name sortKey="Loos, Ruth Jf" sort="Loos, Ruth Jf" uniqKey="Loos R" first="Ruth Jf" last="Loos">Ruth Jf Loos</name><affiliation><nlm:aff id="A11">Medical Research Council (MRC) Epidemiology Unit, Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Lumley, Thomas" sort="Lumley, Thomas" uniqKey="Lumley T" first="Thomas" last="Lumley">Thomas Lumley</name><affiliation><nlm:aff id="A55">Department of Statistics, University of Auckland, Auckland, New Zealand</nlm:aff></affiliation></author><author><name sortKey="Al Balushi, Khalid A" sort="Al Balushi, Khalid A" uniqKey="Al Balushi K" first="Khalid A" last="Al Balushi">Khalid A. Al Balushi</name><affiliation><nlm:aff id="A7">Division of Therapeutics and Molecular Medicine, Nottingham Respiratory Biomedical Research Unit, University Hospital of Nottingham, Nottingham, London, UK</nlm:aff></affiliation></author><author><name sortKey="Ang, Wei Q" sort="Ang, Wei Q" uniqKey="Ang W" first="Wei Q" last="Ang">Wei Q. Ang</name><affiliation><nlm:aff id="A56">School of Women’s and Infants’ Health, The University of Western Australia, Perth, Western Australia, Australia</nlm:aff></affiliation></author><author><name sortKey="Barr, R Graham" sort="Barr, R Graham" uniqKey="Barr R" first="R Graham" last="Barr">R Graham Barr</name><affiliation><nlm:aff id="A57">Department of Medicine, Columbia University Medical Center, New York, New York, USA</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="A58">Department of Surgery and Pathology, University of Western Australia, Nedlands, Western Australia, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A59">PathWest Laboratory Medicine of Western Australia, Queen Elizabeth II Medical Centre, Nedlands, Western Australia, Australia</nlm:aff></affiliation></author><author><name sortKey="Blakey, John D" sort="Blakey, John D" uniqKey="Blakey J" first="John D" last="Blakey">John D. Blakey</name><affiliation><nlm:aff id="A7">Division of Therapeutics and Molecular Medicine, Nottingham Respiratory Biomedical Research Unit, University Hospital of Nottingham, Nottingham, London, UK</nlm:aff></affiliation></author><author><name sortKey="Boban, Mladen" sort="Boban, Mladen" uniqKey="Boban M" first="Mladen" last="Boban">Mladen Boban</name><affiliation><nlm:aff id="A60">Faculty of Medicine, University of Split, Croatia, Split, Croatia</nlm:aff></affiliation></author><author><name sortKey="Boraska, Vesna" sort="Boraska, Vesna" uniqKey="Boraska V" first="Vesna" last="Boraska">Vesna Boraska</name><affiliation><nlm:aff id="A60">Faculty of Medicine, University of Split, Croatia, Split, Croatia</nlm:aff></affiliation></author><author><name sortKey="Brisman, Jonas" sort="Brisman, Jonas" uniqKey="Brisman J" first="Jonas" last="Brisman">Jonas Brisman</name><affiliation><nlm:aff id="A61">Occupational and Environmental Medicine, Department of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden</nlm:aff></affiliation></author><author><name sortKey="Britton, John R" sort="Britton, John R" uniqKey="Britton J" first="John R" last="Britton">John R. Britton</name><affiliation><nlm:aff id="A62">Division of Epidemiology and Public Health, School of Community Health Sciences and Nottingham Respiratory Biomedical Research Unit, University of Nottingham, Nottingham, UK</nlm:aff></affiliation></author><author><name sortKey="Brusselle, Guy G" sort="Brusselle, Guy G" uniqKey="Brusselle G" first="Guy G" last="Brusselle">Guy G. Brusselle</name><affiliation><nlm:aff id="A63">Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium</nlm:aff></affiliation></author><author><name sortKey="Cooper, Cyrus" sort="Cooper, Cyrus" uniqKey="Cooper C" first="Cyrus" last="Cooper">Cyrus Cooper</name><affiliation><nlm:aff id="A64">MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK</nlm:aff></affiliation></author><author><name sortKey="Curjuric, Ivan" sort="Curjuric, Ivan" uniqKey="Curjuric I" first="Ivan" last="Curjuric">Ivan Curjuric</name><affiliation><nlm:aff id="A65">Chronic Disease Epidemiology, Swiss Tropical and Public Health (TPH) Institute, Basel, Switzerland</nlm:aff></affiliation><affiliation><nlm:aff id="A66">University of Basel, Switzerland</nlm:aff></affiliation></author><author><name sortKey="Dahgam, Santosh" sort="Dahgam, Santosh" uniqKey="Dahgam S" first="Santosh" last="Dahgam">Santosh Dahgam</name><affiliation><nlm:aff id="A61">Occupational and Environmental Medicine, Department of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden</nlm:aff></affiliation></author><author><name sortKey="Deary, Ian J" sort="Deary, Ian J" uniqKey="Deary I" first="Ian J" last="Deary">Ian J. Deary</name><affiliation><nlm:aff id="A24">Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A25">Department of Psychology, The University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Ebrahim, Shah" sort="Ebrahim, Shah" uniqKey="Ebrahim S" first="Shah" last="Ebrahim">Shah Ebrahim</name><affiliation><nlm:aff id="A67">Non-Communicable Diseases Epidemiology Unit, Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A68">South Asia Centre for Chronic Disease, New Delhi, India</nlm:aff></affiliation></author><author><name sortKey="Eijgelsheim, Mark" sort="Eijgelsheim, Mark" uniqKey="Eijgelsheim M" first="Mark" last="Eijgelsheim">Mark Eijgelsheim</name><affiliation><nlm:aff id="A3">Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Francks, Clyde" sort="Francks, Clyde" uniqKey="Francks C" first="Clyde" last="Francks">Clyde Francks</name><affiliation><nlm:aff id="A69">Max Planck Institute for Psycholinguistics, Nijmegen, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Gaysina, Darya" sort="Gaysina, Darya" uniqKey="Gaysina D" first="Darya" last="Gaysina">Darya Gaysina</name><affiliation><nlm:aff id="A70">MRC Unit for Lifelong Health and Ageing, London, UK</nlm:aff></affiliation></author><author><name sortKey="Granell, Raquel" sort="Granell, Raquel" uniqKey="Granell R" first="Raquel" last="Granell">Raquel Granell</name><affiliation><nlm:aff id="A71">School of Social and Community Medicine, University of Bristol, Bristol, UK</nlm:aff></affiliation></author><author><name sortKey="Gu, Xiangjun" sort="Gu, Xiangjun" uniqKey="Gu X" first="Xiangjun" last="Gu">Xiangjun Gu</name><affiliation><nlm:aff id="A20">Brown Foundation Institute of Molecular Medicine, University of Texas at Houston, Houston, Texas, USA</nlm:aff></affiliation></author><author><name sortKey="Hankinson, John L" sort="Hankinson, John L" uniqKey="Hankinson J" first="John L" last="Hankinson">John L. Hankinson</name><affiliation><nlm:aff id="A72">Hankinson Consulting, Inc, Athens, Georgia, USA</nlm:aff></affiliation></author><author><name sortKey="Hardy, Rebecca" sort="Hardy, Rebecca" uniqKey="Hardy R" first="Rebecca" last="Hardy">Rebecca Hardy</name><affiliation><nlm:aff id="A70">MRC Unit for Lifelong Health and Ageing, London, UK</nlm:aff></affiliation></author><author><name sortKey="Harris, Sarah E" sort="Harris, Sarah E" uniqKey="Harris S" first="Sarah E" last="Harris">Sarah E. Harris</name><affiliation><nlm:aff id="A24">Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A73">Medical Genetics Section, The University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Henderson, John" sort="Henderson, John" uniqKey="Henderson J" first="John" last="Henderson">John Henderson</name><affiliation><nlm:aff id="A71">School of Social and Community Medicine, University of Bristol, Bristol, UK</nlm:aff></affiliation></author><author><name sortKey="Henry, Amanda" sort="Henry, Amanda" uniqKey="Henry A" first="Amanda" last="Henry">Amanda Henry</name><affiliation><nlm:aff id="A7">Division of Therapeutics and Molecular Medicine, Nottingham Respiratory Biomedical Research Unit, University Hospital of Nottingham, Nottingham, London, UK</nlm:aff></affiliation></author><author><name sortKey="Hingorani, Aroon D" sort="Hingorani, Aroon D" uniqKey="Hingorani A" first="Aroon D" last="Hingorani">Aroon D. Hingorani</name><affiliation><nlm:aff id="A74">Department of Epidemiology and Public Health, University College London, London, UK</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="A3">Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A75">Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Holt, Patrick G" sort="Holt, Patrick G" uniqKey="Holt P" first="Patrick G" last="Holt">Patrick G. Holt</name><affiliation><nlm:aff id="A76">Telethon Institute for Child Health Research and Centre for Child Health Research, The University of Western Australia, Perth, Western Australia, Australia</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="A48">Busselton Population Medical Research Foundation, Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A59">PathWest Laboratory Medicine of Western Australia, Queen Elizabeth II Medical Centre, Nedlands, Western Australia, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A77">School of Pathology and Laboratory Medicine, The University of Western Australia, Nedlands, Western Australia, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A78">School of Population Health, University of Western Australia, Nedlands, Western Australia, Australia</nlm:aff></affiliation></author><author><name sortKey="Hunter, Michael L" sort="Hunter, Michael L" uniqKey="Hunter M" first="Michael L" last="Hunter">Michael L. Hunter</name><affiliation><nlm:aff id="A48">Busselton Population Medical Research Foundation, Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A78">School of Population Health, University of Western Australia, Nedlands, Western Australia, Australia</nlm:aff></affiliation></author><author><name sortKey="Imboden, Medea" sort="Imboden, Medea" uniqKey="Imboden M" first="Medea" last="Imboden">Medea Imboden</name><affiliation><nlm:aff id="A65">Chronic Disease Epidemiology, Swiss Tropical and Public Health (TPH) Institute, Basel, Switzerland</nlm:aff></affiliation><affiliation><nlm:aff id="A66">University of Basel, Switzerland</nlm:aff></affiliation></author><author><name sortKey="Jameson, Karen A" sort="Jameson, Karen A" uniqKey="Jameson K" first="Karen A" last="Jameson">Karen A. Jameson</name><affiliation><nlm:aff id="A64">MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK</nlm:aff></affiliation></author><author><name sortKey="Kerr, Shona M" sort="Kerr, Shona M" uniqKey="Kerr S" first="Shona M" last="Kerr">Shona M. Kerr</name><affiliation><nlm:aff id="A79">Molecular Medicine Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Kolcic, Ivana" sort="Kolcic, Ivana" uniqKey="Kolcic I" first="Ivana" last="Kolcic">Ivana Kolcic</name><affiliation><nlm:aff id="A60">Faculty of Medicine, University of Split, Croatia, Split, Croatia</nlm:aff></affiliation></author><author><name sortKey="Kronenberg, Florian" sort="Kronenberg, Florian" uniqKey="Kronenberg F" first="Florian" last="Kronenberg">Florian Kronenberg</name><affiliation><nlm:aff id="A80">Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria</nlm:aff></affiliation></author><author><name sortKey="Liu, Jason Z" sort="Liu, Jason Z" uniqKey="Liu J" first="Jason Z" last="Liu">Jason Z. Liu</name><affiliation><nlm:aff id="A81">Department of Statistics, University of Oxford, Oxford, UK</nlm:aff></affiliation></author><author><name sortKey="Marchini, Jonathan" sort="Marchini, Jonathan" uniqKey="Marchini J" first="Jonathan" last="Marchini">Jonathan Marchini</name><affiliation><nlm:aff id="A81">Department of Statistics, University of Oxford, Oxford, UK</nlm:aff></affiliation></author><author><name sortKey="Mckeever, Tricia" sort="Mckeever, Tricia" uniqKey="Mckeever T" first="Tricia" last="Mckeever">Tricia Mckeever</name><affiliation><nlm:aff id="A62">Division of Epidemiology and Public Health, School of Community Health Sciences and Nottingham Respiratory Biomedical Research Unit, University of Nottingham, Nottingham, UK</nlm:aff></affiliation></author><author><name sortKey="Morris, Andrew D" sort="Morris, Andrew D" uniqKey="Morris A" first="Andrew D" last="Morris">Andrew D. Morris</name><affiliation><nlm:aff id="A82">Medical Research Institute, The University of Dundee, Dundee, UK</nlm:aff></affiliation></author><author><name sortKey="Olin, Anna Carin" sort="Olin, Anna Carin" uniqKey="Olin A" first="Anna-Carin" last="Olin">Anna-Carin Olin</name><affiliation><nlm:aff id="A61">Occupational and Environmental Medicine, Department of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden</nlm:aff></affiliation></author><author><name sortKey="Porteous, David J" sort="Porteous, David J" uniqKey="Porteous D" first="David J" last="Porteous">David J. Porteous</name><affiliation><nlm:aff id="A79">Molecular Medicine Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Postma, Dirkje S" sort="Postma, Dirkje S" uniqKey="Postma D" first="Dirkje S" last="Postma">Dirkje S. Postma</name><affiliation><nlm:aff id="A83">Department of Pulmonology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Rich, Stephen S" sort="Rich, Stephen S" uniqKey="Rich S" first="Stephen S" last="Rich">Stephen S. Rich</name><affiliation><nlm:aff id="A22">Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, USA</nlm:aff></affiliation></author><author><name sortKey="Ring, Susan M" sort="Ring, Susan M" uniqKey="Ring S" first="Susan M" last="Ring">Susan M. Ring</name><affiliation><nlm:aff id="A71">School of Social and Community Medicine, University of Bristol, Bristol, UK</nlm:aff></affiliation></author><author><name sortKey="Rivadeneira, Fernando" sort="Rivadeneira, Fernando" uniqKey="Rivadeneira F" first="Fernando" last="Rivadeneira">Fernando Rivadeneira</name><affiliation><nlm:aff id="A3">Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A84">Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A75">Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Rochat, Thierry" sort="Rochat, Thierry" uniqKey="Rochat T" first="Thierry" last="Rochat">Thierry Rochat</name><affiliation><nlm:aff id="A85">Division of Pulmonary Medicine, University Hospitals of Geneva, Geneva, Switzerland</nlm:aff></affiliation></author><author><name sortKey="Sayer, Avan Aihie" sort="Sayer, Avan Aihie" uniqKey="Sayer A" first="Avan Aihie" last="Sayer">Avan Aihie Sayer</name><affiliation><nlm:aff id="A64">MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK</nlm:aff></affiliation></author><author><name sortKey="Sayers, Ian" sort="Sayers, Ian" uniqKey="Sayers I" first="Ian" last="Sayers">Ian Sayers</name><affiliation><nlm:aff id="A7">Division of Therapeutics and Molecular Medicine, Nottingham Respiratory Biomedical Research Unit, University Hospital of Nottingham, Nottingham, London, UK</nlm:aff></affiliation></author><author><name sortKey="Sly, Peter D" sort="Sly, Peter D" uniqKey="Sly P" first="Peter D" last="Sly">Peter D. Sly</name><affiliation><nlm:aff id="A76">Telethon Institute for Child Health Research and Centre for Child Health Research, The University of Western Australia, Perth, Western Australia, Australia</nlm:aff></affiliation></author><author><name sortKey="Smith, George Davey" sort="Smith, George Davey" uniqKey="Smith G" first="George Davey" last="Smith">George Davey Smith</name><affiliation><nlm:aff id="A17">MRC Centre for Causal Analyses in Translational Epidemiology, School of Social and Community Medicine, University of Bristol, Bristol, UK</nlm:aff></affiliation></author><author><name sortKey="Sood, Akshay" sort="Sood, Akshay" uniqKey="Sood A" first="Akshay" last="Sood">Akshay Sood</name><affiliation><nlm:aff id="A86">Department of Medicine, University of New Mexico, Albuquerque, New Mexico, USA</nlm:aff></affiliation></author><author><name sortKey="Starr, John M" sort="Starr, John M" uniqKey="Starr J" first="John M" last="Starr">John M. Starr</name><affiliation><nlm:aff id="A24">Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A87">Geriatric Medicine Unit, The University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Uitterlinden, Andre G" sort="Uitterlinden, Andre G" uniqKey="Uitterlinden A" first="André G" last="Uitterlinden">André G. Uitterlinden</name><affiliation><nlm:aff id="A3">Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A84">Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A75">Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Vonk, Judith M" sort="Vonk, Judith M" uniqKey="Vonk J" first="Judith M" last="Vonk">Judith M. Vonk</name><affiliation><nlm:aff id="A88">Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Wannamethee, S Goya" sort="Wannamethee, S Goya" uniqKey="Wannamethee S" first="S Goya" last="Wannamethee">S Goya Wannamethee</name><affiliation><nlm:aff id="A89">Department of Primary Care and Population Health, University College London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Whincup, Peter H" sort="Whincup, Peter H" uniqKey="Whincup P" first="Peter H" last="Whincup">Peter H. Whincup</name><affiliation><nlm:aff id="A90">Division of Population Health Sciences and Education, St George’s University of London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Wijmenga, Cisca" sort="Wijmenga, Cisca" uniqKey="Wijmenga C" first="Cisca" last="Wijmenga">Cisca Wijmenga</name><affiliation><nlm:aff id="A91">Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Williams, O Dale" sort="Williams, O Dale" uniqKey="Williams O" first="O Dale" last="Williams">O Dale Williams</name><affiliation><nlm:aff id="A92">Division of Preventive Medicine, University of Alabama at Birmingham, Birmingham, USA</nlm:aff></affiliation></author><author><name sortKey="Wong, Andrew" sort="Wong, Andrew" uniqKey="Wong A" first="Andrew" last="Wong">Andrew Wong</name><affiliation><nlm:aff id="A70">MRC Unit for Lifelong Health and Ageing, London, UK</nlm:aff></affiliation></author><author><name sortKey="Mangino, Massimo" sort="Mangino, Massimo" uniqKey="Mangino M" first="Massimo" last="Mangino">Massimo Mangino</name><affiliation><nlm:aff id="A9">Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Marciante, Kristin D" sort="Marciante, Kristin D" uniqKey="Marciante K" first="Kristin D" last="Marciante">Kristin D. Marciante</name><affiliation><nlm:aff id="A6">Department of Medicine, University of Washington, Seattle, Washington, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A41">Cardiovascular Health Research Unit, University of Washington, Seattle, Washington, USA</nlm:aff></affiliation></author><author><name sortKey="Mcardle, Wendy L" sort="Mcardle, Wendy L" uniqKey="Mcardle W" first="Wendy L" last="Mcardle">Wendy L. Mcardle</name><affiliation><nlm:aff id="A71">School of Social and Community Medicine, University of Bristol, Bristol, UK</nlm:aff></affiliation></author><author><name sortKey="Meibohm, Bernd" sort="Meibohm, Bernd" uniqKey="Meibohm B" first="Bernd" last="Meibohm">Bernd Meibohm</name><affiliation><nlm:aff id="A93">College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee, USA</nlm:aff></affiliation></author><author><name sortKey="Morrison, Alanna C" sort="Morrison, Alanna C" uniqKey="Morrison A" first="Alanna C" last="Morrison">Alanna C. Morrison</name><affiliation><nlm:aff id="A21">Human Genetics Center, School of Public Health, University of Texas at Houston, Houston, Texas, USA</nlm:aff></affiliation></author><author><name sortKey="North, Kari E" sort="North, Kari E" uniqKey="North K" first="Kari E" last="North">Kari E. North</name><affiliation><nlm:aff id="A33">Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, USA</nlm:aff></affiliation></author><author><name sortKey="Omenaas, Ernst" sort="Omenaas, Ernst" uniqKey="Omenaas E" first="Ernst" last="Omenaas">Ernst Omenaas</name><affiliation><nlm:aff id="A94">Centre for Clinical Research, Haukeland University Hospital, Bergen, Norway</nlm:aff></affiliation></author><author><name sortKey="Palmer, Lyle J" sort="Palmer, Lyle J" uniqKey="Palmer L" first="Lyle J" last="Palmer">Lyle J. Palmer</name><affiliation><nlm:aff id="A18">Genetic Epidemiology and Biostatistics Platform, Ontario Institute for Cancer Research, Toronto, Ontario, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="A19">Prosserman Centre for Health Research, Samuel Lunenfeld Research Institute, Toronto, Ontario, Canada</nlm:aff></affiliation></author><author><name sortKey="Pietil Inen, Kirsi H" sort="Pietil Inen, Kirsi H" uniqKey="Pietil Inen K" first="Kirsi H" last="Pietil Inen">Kirsi H. Pietil Inen</name><affiliation><nlm:aff id="A95">Obesity Research Unit, Department of Medicine, Division of Internal Medicine, Helsinki University Central Hospital, Helsinki, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A96">Hjelt Institute, Department of Public Health, University of Helsinki, Helsinki, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A97">Institute for Molecular Medicine, University of Helsinki, Helsinki, Finland</nlm:aff></affiliation></author><author><name sortKey="Pin, Isabelle" sort="Pin, Isabelle" uniqKey="Pin I" first="Isabelle" last="Pin">Isabelle Pin</name><affiliation><nlm:aff id="A98">Pédiatrie, Centre Hospitalier Universitaire (CHU), Grenoble, France</nlm:aff></affiliation><affiliation><nlm:aff id="A99">Inserm U823, Centre de Recherche Albert Bonniot, Grenoble, France</nlm:aff></affiliation><affiliation><nlm:aff id="A100">Université Joseph Fourier, Grenoble, France</nlm:aff></affiliation></author><author><name sortKey="Polasek, Ozren" sort="Polasek, Ozren" uniqKey="Polasek O" first="Ozren" last="Polašek">Ozren Polašek</name><affiliation><nlm:aff id="A60">Faculty of Medicine, University of Split, Croatia, Split, Croatia</nlm:aff></affiliation><affiliation><nlm:aff id="A101">Gen-Info Ltd, Zagreb, Croatia</nlm:aff></affiliation></author><author><name sortKey="Pouta, Anneli" sort="Pouta, Anneli" uniqKey="Pouta A" first="Anneli" last="Pouta">Anneli Pouta</name><affiliation><nlm:aff id="A102">Department of Children, Young People and Families, National Institute for Health and Welfare, Oulu, Finland</nlm:aff></affiliation></author><author><name sortKey="Psaty, Bruce M" sort="Psaty, Bruce M" uniqKey="Psaty B" first="Bruce M" last="Psaty">Bruce M. Psaty</name><affiliation><nlm:aff id="A6">Department of Medicine, University of Washington, Seattle, Washington, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A41">Cardiovascular Health Research Unit, University of Washington, Seattle, Washington, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A42">Department of Epidemiology, University of Washington, Seattle, Washington, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A43">Group Health Research Institute, Group Health Cooperative, Seattle, Washington, USA</nlm:aff></affiliation></author><author><name sortKey="Hartikainen, Anna Liisa" sort="Hartikainen, Anna Liisa" uniqKey="Hartikainen A" first="Anna-Liisa" last="Hartikainen">Anna-Liisa Hartikainen</name><affiliation><nlm:aff id="A103">Institute of Clinical Medicine, University of Oulu, Oulu, Finland</nlm:aff></affiliation></author><author><name sortKey="Rantanen, Taina" sort="Rantanen, Taina" uniqKey="Rantanen T" first="Taina" last="Rantanen">Taina Rantanen</name><affiliation><nlm:aff id="A104"> Gerontology Research Centre, Department of Health Sciences, University of Jyväskylä, Jyväskylä, Finland</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="A97">Institute for Molecular Medicine, University of Helsinki, Helsinki, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A105">Public Health Genomics Unit, Department Of Chronic Disease Prevention, The National Institute for Health and Welfare, Helsinki, Finland</nlm:aff></affiliation></author><author><name sortKey="Rotter, Jerome I" sort="Rotter, Jerome I" uniqKey="Rotter J" first="Jerome I" last="Rotter">Jerome I. Rotter</name><affiliation><nlm:aff id="A106">Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA</nlm:aff></affiliation></author><author><name sortKey="Rudan, Igor" sort="Rudan, Igor" uniqKey="Rudan I" first="Igor" last="Rudan">Igor Rudan</name><affiliation><nlm:aff id="A31">Centre for Population Health Sciences, The University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A35">Croatian Centre for Global Health, The University of Split Medical School, Split, Croatia</nlm:aff></affiliation><affiliation><nlm:aff id="A101">Gen-Info Ltd, Zagreb, Croatia</nlm:aff></affiliation></author><author><name sortKey="Rudnicka, Alicja R" sort="Rudnicka, Alicja R" uniqKey="Rudnicka A" first="Alicja R" last="Rudnicka">Alicja R. Rudnicka</name><affiliation><nlm:aff id="A90">Division of Population Health Sciences and Education, St George’s University of London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Schulz, Holger" sort="Schulz, Holger" uniqKey="Schulz H" first="Holger" last="Schulz">Holger Schulz</name><affiliation><nlm:aff id="A107">Institute of Epidemiology I, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany</nlm:aff></affiliation></author><author><name sortKey="Shin, So Youn" sort="Shin, So Youn" uniqKey="Shin S" first="So-Youn" last="Shin">So-Youn Shin</name><affiliation><nlm:aff id="A29">Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Spector, Tim D" sort="Spector, Tim D" uniqKey="Spector T" first="Tim D" last="Spector">Tim D. Spector</name><affiliation><nlm:aff id="A9">Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Surakka, Ida" sort="Surakka, Ida" uniqKey="Surakka I" first="Ida" last="Surakka">Ida Surakka</name><affiliation><nlm:aff id="A97">Institute for Molecular Medicine, University of Helsinki, Helsinki, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A105">Public Health Genomics Unit, Department Of Chronic Disease Prevention, The National Institute for Health and Welfare, Helsinki, Finland</nlm:aff></affiliation></author><author><name sortKey="Vitart, Veronique" sort="Vitart, Veronique" uniqKey="Vitart V" first="Veronique" last="Vitart">Veronique Vitart</name><affiliation><nlm:aff id="A14">MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Volzke, Henry" sort="Volzke, Henry" uniqKey="Volzke H" first="Henry" last="Völzke">Henry Völzke</name><affiliation><nlm:aff id="A108">Institute for Community Medicine, Study of Health In Pomerania (SHIP)/Clinical Epidemiological Research, University of Greifswald, Greifswald, Germany</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="A11">Medical Research Council (MRC) Epidemiology Unit, Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Warrington, Nicole M" sort="Warrington, Nicole M" uniqKey="Warrington N" first="Nicole M" last="Warrington">Nicole M. Warrington</name><affiliation><nlm:aff id="A56">School of Women’s and Infants’ Health, The University of Western Australia, Perth, Western Australia, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A19">Prosserman Centre for Health Research, Samuel Lunenfeld Research Institute, Toronto, Ontario, Canada</nlm:aff></affiliation></author><author><name sortKey="Wichmann, H Erich" sort="Wichmann, H Erich" uniqKey="Wichmann H" first="H-Erich" last="Wichmann">H-Erich Wichmann</name><affiliation><nlm:aff id="A107">Institute of Epidemiology I, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A109">Institute of Medical Informatics, Biometry and Epidemiology, Chair of Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A110">Klinikum Grosshadern, Munich, Germany</nlm:aff></affiliation></author><author><name sortKey="Wild, Sarah H" sort="Wild, Sarah H" uniqKey="Wild S" first="Sarah H" last="Wild">Sarah H. Wild</name><affiliation><nlm:aff id="A31">Centre for Population Health Sciences, The University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Wilk, Jemma B" sort="Wilk, Jemma B" uniqKey="Wilk J" first="Jemma B" last="Wilk">Jemma B. Wilk</name><affiliation><nlm:aff id="A111">Division of Aging, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Wjst, Matthias" sort="Wjst, Matthias" uniqKey="Wjst M" first="Matthias" last="Wjst">Matthias Wjst</name><affiliation><nlm:aff id="A112">Institute of Lung Biology and Disease, Comprehensive Pneumology Center, Helmholtz Zentrum München, Neuherberg, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A113">Institute for Medical Statistics and Epidemiology (IMSE), Technical University Munich, Munich, Germany</nlm:aff></affiliation></author><author><name sortKey="Wright, Alan F" sort="Wright, Alan F" uniqKey="Wright A" first="Alan F" last="Wright">Alan F. Wright</name><affiliation><nlm:aff id="A14">MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Zgaga, Lina" sort="Zgaga, Lina" uniqKey="Zgaga L" first="Lina" last="Zgaga">Lina Zgaga</name><affiliation><nlm:aff id="A114">Andrija Stampar School of Public Health, Faculty of Medicine, University of Zagreb, Zagreb, Croatia</nlm:aff></affiliation><affiliation><nlm:aff id="A31">Centre for Population Health Sciences, The University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Zemunik, Tatijana" sort="Zemunik, Tatijana" uniqKey="Zemunik T" first="Tatijana" last="Zemunik">Tatijana Zemunik</name><affiliation><nlm:aff id="A60">Faculty of Medicine, University of Split, Croatia, Split, Croatia</nlm:aff></affiliation></author><author><name sortKey="Pennell, Craig E" sort="Pennell, Craig E" uniqKey="Pennell C" first="Craig E" last="Pennell">Craig E. Pennell</name><affiliation><nlm:aff id="A56">School of Women’s and Infants’ Health, The University of Western Australia, Perth, Western Australia, Australia</nlm:aff></affiliation></author><author><name sortKey="Nyberg, Fredrik" sort="Nyberg, Fredrik" uniqKey="Nyberg F" first="Fredrik" last="Nyberg">Fredrik Nyberg</name><affiliation><nlm:aff id="A61">Occupational and Environmental Medicine, Department of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden</nlm:aff></affiliation><affiliation><nlm:aff id="A115">AstraZeneca Research and Development, Mölndal, Sweden</nlm:aff></affiliation></author><author><name sortKey="Kuh, Diana" sort="Kuh, Diana" uniqKey="Kuh D" first="Diana" last="Kuh">Diana Kuh</name><affiliation><nlm:aff id="A70">MRC Unit for Lifelong Health and Ageing, London, UK</nlm:aff></affiliation></author><author><name sortKey="Holloway, John W" sort="Holloway, John W" uniqKey="Holloway J" first="John W" last="Holloway">John W. Holloway</name><affiliation><nlm:aff id="A116">Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A117">Infection, Inflammation and Immunity, Faculty of Medicine, University of Southampton, Southampton, UK</nlm:aff></affiliation></author><author><name sortKey="Boezen, H Marike" sort="Boezen, H Marike" uniqKey="Boezen H" first="H Marike" last="Boezen">H Marike Boezen</name><affiliation><nlm:aff id="A88">Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Lawlor, Debbie A" sort="Lawlor, Debbie A" uniqKey="Lawlor D" first="Debbie A" last="Lawlor">Debbie A. Lawlor</name><affiliation><nlm:aff id="A17">MRC Centre for Causal Analyses in Translational Epidemiology, School of Social and Community Medicine, University of Bristol, Bristol, UK</nlm:aff></affiliation></author><author><name sortKey="Morris, Richard W" sort="Morris, Richard W" uniqKey="Morris R" first="Richard W" last="Morris">Richard W. Morris</name><affiliation><nlm:aff id="A89">Department of Primary Care and Population Health, University College London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Probst Hensch, Nicole" sort="Probst Hensch, Nicole" uniqKey="Probst Hensch N" first="Nicole" last="Probst-Hensch">Nicole Probst-Hensch</name><affiliation><nlm:aff id="A65">Chronic Disease Epidemiology, Swiss Tropical and Public Health (TPH) Institute, Basel, Switzerland</nlm:aff></affiliation><affiliation><nlm:aff id="A66">University of Basel, Switzerland</nlm:aff></affiliation></author><author><name sortKey="Kaprio, Jaakko" sort="Kaprio, Jaakko" uniqKey="Kaprio J" first="Jaakko" last="Kaprio">Jaakko Kaprio</name><affiliation><nlm:aff id="A44">National Institute for Health and Welfare, Helsinki, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A96">Hjelt Institute, Department of Public Health, University of Helsinki, Helsinki, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A97">Institute for Molecular Medicine, University of Helsinki, Helsinki, Finland</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="A31">Centre for Population Health Sciences, The University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Hayward, Caroline" sort="Hayward, Caroline" uniqKey="Hayward C" first="Caroline" last="Hayward">Caroline Hayward</name><affiliation><nlm:aff id="A14">MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="K Honen, Mika" sort="K Honen, Mika" uniqKey="K Honen M" first="Mika" last="K Hönen">Mika K Hönen</name><affiliation><nlm:aff id="A118">Department of Clinical Physiology, University of Tampere and Tampere University Hospital, Tampere, Finland</nlm:aff></affiliation></author><author><name sortKey="Heinrich, Joachim" sort="Heinrich, Joachim" uniqKey="Heinrich J" first="Joachim" last="Heinrich">Joachim Heinrich</name><affiliation><nlm:aff id="A107">Institute of Epidemiology I, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany</nlm:aff></affiliation></author><author><name sortKey="Musk, Arthur W" sort="Musk, Arthur W" uniqKey="Musk A" first="Arthur W" last="Musk">Arthur W. Musk</name><affiliation><nlm:aff id="A48">Busselton Population Medical Research Foundation, Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A119">Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A78">School of Population Health, University of Western Australia, Nedlands, Western Australia, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A47">The School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia</nlm:aff></affiliation></author><author><name sortKey="Jarvis, Deborah L" sort="Jarvis, Deborah L" uniqKey="Jarvis D" first="Deborah L" last="Jarvis">Deborah L. Jarvis</name><affiliation><nlm:aff id="A38"> Respiratory Epidemiology and Public Health, Imperial College London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A120">MRC Health Protection Agency (HPA) Centre for Environment and Health, Imperial College London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Gl Ser, Sven" sort="Gl Ser, Sven" uniqKey="Gl Ser S" first="Sven" last="Gl Ser">Sven Gl Ser</name><affiliation><nlm:aff id="A121">University Hospital Greifswald, Department of Internal Medicine B, Greifswald, Germany</nlm:aff></affiliation></author><author><name sortKey="J Rvelin, Marjo Riitta" sort="J Rvelin, Marjo Riitta" uniqKey="J Rvelin M" first="Marjo-Riitta" last="J Rvelin">Marjo-Riitta J Rvelin</name><affiliation><nlm:aff id="A39">Department of Epidemiology and Biostatistics, Imperial College London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A122">Institute of Health Sciences, University of Oulu, Oulu, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A123">Biocenter Oulu, University of Oulu, Oulu, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A102">Department of Children, Young People and Families, National Institute for Health and Welfare, Oulu, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A120">MRC Health Protection Agency (HPA) Centre for Environment and Health, Imperial College London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Stricker, Bruno H Ch" sort="Stricker, Bruno H Ch" uniqKey="Stricker B" first="Bruno H Ch" last="Stricker">Bruno H Ch Stricker</name><affiliation><nlm:aff id="A3">Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Inspectorate of Healthcare, The Hague, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A84">Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A75">Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A124">Department of Medical Informatics, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Elliott, Paul" sort="Elliott, Paul" uniqKey="Elliott P" first="Paul" last="Elliott">Paul Elliott</name><affiliation><nlm:aff id="A120">MRC Health Protection Agency (HPA) Centre for Environment and Health, Imperial College London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A39">Department of Epidemiology and Biostatistics, Imperial College London, London, UK</nlm:aff></affiliation></author><author><name sortKey="O Onnor, George T" sort="O Onnor, George T" uniqKey="O Onnor G" first="George T" last="O Onnor">George T. O Onnor</name><affiliation><nlm:aff id="A125">Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A126">The National Heart, Lung and Blood Institute’s Framingham Heart Study, Framingham, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Strachan, David P" sort="Strachan, David P" uniqKey="Strachan D" first="David P" last="Strachan">David P. Strachan</name><affiliation><nlm:aff id="A90">Division of Population Health Sciences and Education, St George’s University of London, London, UK</nlm:aff></affiliation></author><author><name sortKey="London, Stephanie J" sort="London, Stephanie J" uniqKey="London S" first="Stephanie J" last="London">Stephanie J. London</name><affiliation><nlm:aff id="A36">Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA</nlm:aff></affiliation></author><author><name sortKey="Hall, Ian P" sort="Hall, Ian P" uniqKey="Hall I" first="Ian P" last="Hall">Ian P. Hall</name><affiliation><nlm:aff id="A7">Division of Therapeutics and Molecular Medicine, Nottingham Respiratory Biomedical Research Unit, University Hospital of Nottingham, Nottingham, London, UK</nlm:aff></affiliation></author><author><name sortKey="Gudnason, Vilmundur" sort="Gudnason, Vilmundur" uniqKey="Gudnason V" first="Vilmundur" last="Gudnason">Vilmundur Gudnason</name><affiliation><nlm:aff id="A12">Icelandic Heart Association, Kopavogur, Iceland</nlm:aff></affiliation><affiliation><nlm:aff id="A13">University of Iceland, Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Tobin, Martin D" sort="Tobin, Martin D" uniqKey="Tobin M" first="Martin D" last="Tobin">Martin D. Tobin</name><affiliation><nlm:aff id="A1">Department of Health Sciences, University of Leicester, Leicester, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Genetics, University of Leicester, Leicester, UK</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">21946350</idno><idno type="pmc">3267376</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3267376</idno><idno type="RBID">PMC:3267376</idno><idno type="doi">10.1038/ng.941</idno><date when="2011">2011</date><idno type="wicri:Area/Pmc/Corpus">002E07</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002E07</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Genome-wide association and large scale follow-up identifies 16 new loci influencing lung function</title><author><name sortKey="Artigas, Maria Soler" sort="Artigas, Maria Soler" uniqKey="Artigas M" first="María Soler" last="Artigas">María Soler Artigas</name><affiliation><nlm:aff id="A1">Department of Health Sciences, University of Leicester, Leicester, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Genetics, University of Leicester, Leicester, UK</nlm:aff></affiliation></author><author><name sortKey="Loth, Daan W" sort="Loth, Daan W" uniqKey="Loth D" first="Daan W" last="Loth">Daan W. Loth</name><affiliation><nlm:aff id="A3">Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Inspectorate of Healthcare, The Hague, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Wain, Louise V" sort="Wain, Louise V" uniqKey="Wain L" first="Louise V" last="Wain">Louise V. Wain</name><affiliation><nlm:aff id="A1">Department of Health Sciences, University of Leicester, Leicester, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Genetics, University of Leicester, Leicester, UK</nlm:aff></affiliation></author><author><name sortKey="Gharib, Sina A" sort="Gharib, Sina A" uniqKey="Gharib S" first="Sina A" last="Gharib">Sina A. Gharib</name><affiliation><nlm:aff id="A5">Center for Lung Biology, University of Washington, Seattle, Washington, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A6">Department of Medicine, University of Washington, Seattle, Washington, USA</nlm:aff></affiliation></author><author><name sortKey="Obeidat, Ma N" sort="Obeidat, Ma N" uniqKey="Obeidat M" first="Ma N" last="Obeidat">Ma N Obeidat</name><affiliation><nlm:aff id="A7">Division of Therapeutics and Molecular Medicine, Nottingham Respiratory Biomedical Research Unit, University Hospital of Nottingham, Nottingham, London, UK</nlm:aff></affiliation></author><author><name sortKey="Tang, Wenbo" sort="Tang, Wenbo" uniqKey="Tang W" first="Wenbo" last="Tang">Wenbo Tang</name><affiliation><nlm:aff id="A8">Division of Nutritional Sciences, Cornell University Ithaca, New York, USA</nlm:aff></affiliation></author><author><name sortKey="Zhai, Guangju" sort="Zhai, Guangju" uniqKey="Zhai G" first="Guangju" last="Zhai">Guangju Zhai</name><affiliation><nlm:aff id="A9">Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A10">Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, Newfoundland, Canada</nlm:aff></affiliation></author><author><name sortKey="Zhao, Jing Hua" sort="Zhao, Jing Hua" uniqKey="Zhao J" first="Jing Hua" last="Zhao">Jing Hua Zhao</name><affiliation><nlm:aff id="A11">Medical Research Council (MRC) Epidemiology Unit, Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Smith, Albert Vernon" sort="Smith, Albert Vernon" uniqKey="Smith A" first="Albert Vernon" last="Smith">Albert Vernon Smith</name><affiliation><nlm:aff id="A12">Icelandic Heart Association, Kopavogur, Iceland</nlm:aff></affiliation><affiliation><nlm:aff id="A13">University of Iceland, Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Huffman, Jennifer E" sort="Huffman, Jennifer E" uniqKey="Huffman J" first="Jennifer E" last="Huffman">Jennifer E. Huffman</name><affiliation><nlm:aff id="A14">MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Albrecht, Eva" sort="Albrecht, Eva" uniqKey="Albrecht E" first="Eva" last="Albrecht">Eva Albrecht</name><affiliation><nlm:aff id="A15">Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany</nlm:aff></affiliation></author><author><name sortKey="Jackson, Catherine M" sort="Jackson, Catherine M" uniqKey="Jackson C" first="Catherine M" last="Jackson">Catherine M. Jackson</name><affiliation><nlm:aff id="A16">School of Medicine, University of St. Andrews, St. Andrews, Scotland, UK</nlm:aff></affiliation></author><author><name sortKey="Evans, David M" sort="Evans, David M" uniqKey="Evans D" first="David M" last="Evans">David M. Evans</name><affiliation><nlm:aff id="A17">MRC Centre for Causal Analyses in Translational Epidemiology, School of Social and Community Medicine, University of Bristol, Bristol, UK</nlm:aff></affiliation></author><author><name sortKey="Cadby, Gemma" sort="Cadby, Gemma" uniqKey="Cadby G" first="Gemma" last="Cadby">Gemma Cadby</name><affiliation><nlm:aff id="A18">Genetic Epidemiology and Biostatistics Platform, Ontario Institute for Cancer Research, Toronto, Ontario, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="A19">Prosserman Centre for Health Research, Samuel Lunenfeld Research Institute, Toronto, Ontario, Canada</nlm:aff></affiliation></author><author><name sortKey="Fornage, Myriam" sort="Fornage, Myriam" uniqKey="Fornage M" first="Myriam" last="Fornage">Myriam Fornage</name><affiliation><nlm:aff id="A20">Brown Foundation Institute of Molecular Medicine, University of Texas at Houston, Houston, Texas, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A21">Human Genetics Center, School of Public Health, University of Texas at Houston, Houston, Texas, USA</nlm:aff></affiliation></author><author><name sortKey="Manichaikul, Ani" sort="Manichaikul, Ani" uniqKey="Manichaikul A" first="Ani" last="Manichaikul">Ani Manichaikul</name><affiliation><nlm:aff id="A22">Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A23">Department of Public Health Sciences, Division of Biostatistics and Epidemiology, University of Virginia, Charlottesville, Virginia, USA</nlm:aff></affiliation></author><author><name sortKey="Lopez, Lorna M" sort="Lopez, Lorna M" uniqKey="Lopez L" first="Lorna M" last="Lopez">Lorna M. Lopez</name><affiliation><nlm:aff id="A24">Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A25">Department of Psychology, The University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Johnson, Toby" sort="Johnson, Toby" uniqKey="Johnson T" first="Toby" last="Johnson">Toby Johnson</name><affiliation><nlm:aff id="A26">Clinical Pharmacology and the Genome Centre, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Aldrich, Melinda C" sort="Aldrich, Melinda C" uniqKey="Aldrich M" first="Melinda C" last="Aldrich">Melinda C. Aldrich</name><affiliation><nlm:aff id="A27">Department of Thoracic Surgery, Vanderbilt University, Nashville, Tennessee, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A28">Division of Epidemiology, Vanderbilt University, Nashville, Tennessee, USA</nlm:aff></affiliation></author><author><name sortKey="Aspelund, Thor" sort="Aspelund, Thor" uniqKey="Aspelund T" first="Thor" last="Aspelund">Thor Aspelund</name><affiliation><nlm:aff id="A12">Icelandic Heart Association, Kopavogur, Iceland</nlm:aff></affiliation><affiliation><nlm:aff id="A13">University of Iceland, Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Barroso, Ines" sort="Barroso, Ines" uniqKey="Barroso I" first="Inês" last="Barroso">Inês Barroso</name><affiliation><nlm:aff id="A29">Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A30">University of Cambridge Metabolic Research Labs, Institute of Metabolic Science Addenbrooke’s Hospital, Cambridge, 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="A31">Centre for Population Health Sciences, The University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Cassano, Patricia A" sort="Cassano, Patricia A" uniqKey="Cassano P" first="Patricia A" last="Cassano">Patricia A. Cassano</name><affiliation><nlm:aff id="A8">Division of Nutritional Sciences, Cornell University Ithaca, New York, 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="A32">Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, USA</nlm:aff></affiliation></author><author><name sortKey="Eiriksdottir, Gudny" sort="Eiriksdottir, Gudny" uniqKey="Eiriksdottir G" first="Gudny" last="Eiriksdottir">Gudny Eiriksdottir</name><affiliation><nlm:aff id="A12">Icelandic Heart Association, Kopavogur, Iceland</nlm:aff></affiliation></author><author><name sortKey="Franceschini, Nora" sort="Franceschini, Nora" uniqKey="Franceschini N" first="Nora" last="Franceschini">Nora Franceschini</name><affiliation><nlm:aff id="A33">Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, USA</nlm:aff></affiliation></author><author><name sortKey="Garcia, Melissa" sort="Garcia, Melissa" uniqKey="Garcia M" first="Melissa" last="Garcia">Melissa Garcia</name><affiliation><nlm:aff id="A34">Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA</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="A15">Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany</nlm:aff></affiliation></author><author><name sortKey="Gislason, Gauti Kjartan" sort="Gislason, Gauti Kjartan" uniqKey="Gislason G" first="Gauti Kjartan" last="Gislason">Gauti Kjartan Gislason</name><affiliation><nlm:aff id="A12">Icelandic Heart Association, Kopavogur, Iceland</nlm:aff></affiliation></author><author><name sortKey="Grkovic, Ivica" sort="Grkovic, Ivica" uniqKey="Grkovic I" first="Ivica" last="Grkovic">Ivica Grkovic</name><affiliation><nlm:aff id="A35">Croatian Centre for Global Health, The University of Split Medical School, Split, Croatia</nlm:aff></affiliation></author><author><name sortKey="Hammond, Christopher J" sort="Hammond, Christopher J" uniqKey="Hammond C" first="Christopher J" last="Hammond">Christopher J. Hammond</name><affiliation><nlm:aff id="A9">Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Hancock, Dana B" sort="Hancock, Dana B" uniqKey="Hancock D" first="Dana B" last="Hancock">Dana B. Hancock</name><affiliation><nlm:aff id="A36">Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A37">Behavioral Health Epidemiology Program, Research Triangle Institute International, Research Triangle Park, North Carolina, USA</nlm:aff></affiliation></author><author><name sortKey="Harris, Tamara B" sort="Harris, Tamara B" uniqKey="Harris T" first="Tamara B" last="Harris">Tamara B. Harris</name><affiliation><nlm:aff id="A34">Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA</nlm:aff></affiliation></author><author><name sortKey="Ramasamy, Adaikalavan" sort="Ramasamy, Adaikalavan" uniqKey="Ramasamy A" first="Adaikalavan" last="Ramasamy">Adaikalavan Ramasamy</name><affiliation><nlm:aff id="A38"> Respiratory Epidemiology and Public Health, Imperial College London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A39">Department of Epidemiology and Biostatistics, Imperial College London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A40">Department of Medical and Molecular Genetics, King’s College London, Guy’s Hospital, London, UK</nlm:aff></affiliation></author><author><name sortKey="Heckbert, Susan R" sort="Heckbert, Susan R" uniqKey="Heckbert S" first="Susan R" last="Heckbert">Susan R. Heckbert</name><affiliation><nlm:aff id="A41">Cardiovascular Health Research Unit, University of Washington, Seattle, Washington, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A42">Department of Epidemiology, University of Washington, Seattle, Washington, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A43">Group Health Research Institute, Group Health Cooperative, Seattle, Washington, USA</nlm:aff></affiliation></author><author><name sortKey="Heliovaara, Markku" sort="Heliovaara, Markku" uniqKey="Heliovaara M" first="Markku" last="Heliövaara">Markku Heliövaara</name><affiliation><nlm:aff id="A44">National Institute for Health and Welfare, Helsinki, Finland</nlm:aff></affiliation></author><author><name sortKey="Homuth, Georg" sort="Homuth, Georg" uniqKey="Homuth G" first="Georg" last="Homuth">Georg Homuth</name><affiliation><nlm:aff id="A45">Interfaculty Institute for Genetics and Functional Genomics, Department of Functional Genomics, University of Greifswald, Greifswald, Germany</nlm:aff></affiliation></author><author><name sortKey="Hysi, Pirro G" sort="Hysi, Pirro G" uniqKey="Hysi P" first="Pirro G" last="Hysi">Pirro G. Hysi</name><affiliation><nlm:aff id="A9">Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK</nlm:aff></affiliation></author><author><name sortKey="James, Alan L" sort="James, Alan L" uniqKey="James A" first="Alan L" last="James">Alan L. James</name><affiliation><nlm:aff id="A46">Department of Pulmonary Physiology and Sleep Medicine/West Australian Sleep Disorders Research Institute, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A47">The School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A48">Busselton Population Medical Research Foundation, Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia</nlm:aff></affiliation></author><author><name sortKey="Jankovic, Stipan" sort="Jankovic, Stipan" uniqKey="Jankovic S" first="Stipan" last="Jankovic">Stipan Jankovic</name><affiliation><nlm:aff id="A35">Croatian Centre for Global Health, The University of Split Medical School, Split, Croatia</nlm:aff></affiliation></author><author><name sortKey="Joubert, Bonnie R" sort="Joubert, Bonnie R" uniqKey="Joubert B" first="Bonnie R" last="Joubert">Bonnie R. Joubert</name><affiliation><nlm:aff id="A36">Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA</nlm:aff></affiliation></author><author><name sortKey="Karrasch, Stefan" sort="Karrasch, Stefan" uniqKey="Karrasch S" first="Stefan" last="Karrasch">Stefan Karrasch</name><affiliation><nlm:aff id="A49">Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, Ludwig-Maximilians-University, Munich, 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="A50">Unit for Molecular Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany</nlm:aff></affiliation></author><author><name sortKey="Koch, Beate" sort="Koch, Beate" uniqKey="Koch B" first="Beate" last="Koch">Beate Koch</name><affiliation><nlm:aff id="A51">Department of Internal Medicine B, University Hospital Greifswald, Greifswald, Germany</nlm:aff></affiliation></author><author><name sortKey="Kritchevsky, Stephen B" sort="Kritchevsky, Stephen B" uniqKey="Kritchevsky S" first="Stephen B" last="Kritchevsky">Stephen B. Kritchevsky</name><affiliation><nlm:aff id="A52">Sticht Center on Aging, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA</nlm:aff></affiliation></author><author><name sortKey="Launer, Lenore J" sort="Launer, Lenore J" uniqKey="Launer L" first="Lenore J" last="Launer">Lenore J. Launer</name><affiliation><nlm:aff id="A34">Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA</nlm:aff></affiliation></author><author><name sortKey="Liu, Yongmei" sort="Liu, Yongmei" uniqKey="Liu Y" first="Yongmei" last="Liu">Yongmei Liu</name><affiliation><nlm:aff id="A53">Epidemiology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA</nlm:aff></affiliation></author><author><name sortKey="Loehr, Laura R" sort="Loehr, Laura R" uniqKey="Loehr L" first="Laura R" last="Loehr">Laura R. Loehr</name><affiliation><nlm:aff id="A33">Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, USA</nlm:aff></affiliation></author><author><name sortKey="Lohman, Kurt" sort="Lohman, Kurt" uniqKey="Lohman K" first="Kurt" last="Lohman">Kurt Lohman</name><affiliation><nlm:aff id="A54">Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA</nlm:aff></affiliation></author><author><name sortKey="Loos, Ruth Jf" sort="Loos, Ruth Jf" uniqKey="Loos R" first="Ruth Jf" last="Loos">Ruth Jf Loos</name><affiliation><nlm:aff id="A11">Medical Research Council (MRC) Epidemiology Unit, Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Lumley, Thomas" sort="Lumley, Thomas" uniqKey="Lumley T" first="Thomas" last="Lumley">Thomas Lumley</name><affiliation><nlm:aff id="A55">Department of Statistics, University of Auckland, Auckland, New Zealand</nlm:aff></affiliation></author><author><name sortKey="Al Balushi, Khalid A" sort="Al Balushi, Khalid A" uniqKey="Al Balushi K" first="Khalid A" last="Al Balushi">Khalid A. Al Balushi</name><affiliation><nlm:aff id="A7">Division of Therapeutics and Molecular Medicine, Nottingham Respiratory Biomedical Research Unit, University Hospital of Nottingham, Nottingham, London, UK</nlm:aff></affiliation></author><author><name sortKey="Ang, Wei Q" sort="Ang, Wei Q" uniqKey="Ang W" first="Wei Q" last="Ang">Wei Q. Ang</name><affiliation><nlm:aff id="A56">School of Women’s and Infants’ Health, The University of Western Australia, Perth, Western Australia, Australia</nlm:aff></affiliation></author><author><name sortKey="Barr, R Graham" sort="Barr, R Graham" uniqKey="Barr R" first="R Graham" last="Barr">R Graham Barr</name><affiliation><nlm:aff id="A57">Department of Medicine, Columbia University Medical Center, New York, New York, USA</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="A58">Department of Surgery and Pathology, University of Western Australia, Nedlands, Western Australia, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A59">PathWest Laboratory Medicine of Western Australia, Queen Elizabeth II Medical Centre, Nedlands, Western Australia, Australia</nlm:aff></affiliation></author><author><name sortKey="Blakey, John D" sort="Blakey, John D" uniqKey="Blakey J" first="John D" last="Blakey">John D. Blakey</name><affiliation><nlm:aff id="A7">Division of Therapeutics and Molecular Medicine, Nottingham Respiratory Biomedical Research Unit, University Hospital of Nottingham, Nottingham, London, UK</nlm:aff></affiliation></author><author><name sortKey="Boban, Mladen" sort="Boban, Mladen" uniqKey="Boban M" first="Mladen" last="Boban">Mladen Boban</name><affiliation><nlm:aff id="A60">Faculty of Medicine, University of Split, Croatia, Split, Croatia</nlm:aff></affiliation></author><author><name sortKey="Boraska, Vesna" sort="Boraska, Vesna" uniqKey="Boraska V" first="Vesna" last="Boraska">Vesna Boraska</name><affiliation><nlm:aff id="A60">Faculty of Medicine, University of Split, Croatia, Split, Croatia</nlm:aff></affiliation></author><author><name sortKey="Brisman, Jonas" sort="Brisman, Jonas" uniqKey="Brisman J" first="Jonas" last="Brisman">Jonas Brisman</name><affiliation><nlm:aff id="A61">Occupational and Environmental Medicine, Department of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden</nlm:aff></affiliation></author><author><name sortKey="Britton, John R" sort="Britton, John R" uniqKey="Britton J" first="John R" last="Britton">John R. Britton</name><affiliation><nlm:aff id="A62">Division of Epidemiology and Public Health, School of Community Health Sciences and Nottingham Respiratory Biomedical Research Unit, University of Nottingham, Nottingham, UK</nlm:aff></affiliation></author><author><name sortKey="Brusselle, Guy G" sort="Brusselle, Guy G" uniqKey="Brusselle G" first="Guy G" last="Brusselle">Guy G. Brusselle</name><affiliation><nlm:aff id="A63">Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium</nlm:aff></affiliation></author><author><name sortKey="Cooper, Cyrus" sort="Cooper, Cyrus" uniqKey="Cooper C" first="Cyrus" last="Cooper">Cyrus Cooper</name><affiliation><nlm:aff id="A64">MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK</nlm:aff></affiliation></author><author><name sortKey="Curjuric, Ivan" sort="Curjuric, Ivan" uniqKey="Curjuric I" first="Ivan" last="Curjuric">Ivan Curjuric</name><affiliation><nlm:aff id="A65">Chronic Disease Epidemiology, Swiss Tropical and Public Health (TPH) Institute, Basel, Switzerland</nlm:aff></affiliation><affiliation><nlm:aff id="A66">University of Basel, Switzerland</nlm:aff></affiliation></author><author><name sortKey="Dahgam, Santosh" sort="Dahgam, Santosh" uniqKey="Dahgam S" first="Santosh" last="Dahgam">Santosh Dahgam</name><affiliation><nlm:aff id="A61">Occupational and Environmental Medicine, Department of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden</nlm:aff></affiliation></author><author><name sortKey="Deary, Ian J" sort="Deary, Ian J" uniqKey="Deary I" first="Ian J" last="Deary">Ian J. Deary</name><affiliation><nlm:aff id="A24">Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A25">Department of Psychology, The University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Ebrahim, Shah" sort="Ebrahim, Shah" uniqKey="Ebrahim S" first="Shah" last="Ebrahim">Shah Ebrahim</name><affiliation><nlm:aff id="A67">Non-Communicable Diseases Epidemiology Unit, Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A68">South Asia Centre for Chronic Disease, New Delhi, India</nlm:aff></affiliation></author><author><name sortKey="Eijgelsheim, Mark" sort="Eijgelsheim, Mark" uniqKey="Eijgelsheim M" first="Mark" last="Eijgelsheim">Mark Eijgelsheim</name><affiliation><nlm:aff id="A3">Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Francks, Clyde" sort="Francks, Clyde" uniqKey="Francks C" first="Clyde" last="Francks">Clyde Francks</name><affiliation><nlm:aff id="A69">Max Planck Institute for Psycholinguistics, Nijmegen, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Gaysina, Darya" sort="Gaysina, Darya" uniqKey="Gaysina D" first="Darya" last="Gaysina">Darya Gaysina</name><affiliation><nlm:aff id="A70">MRC Unit for Lifelong Health and Ageing, London, UK</nlm:aff></affiliation></author><author><name sortKey="Granell, Raquel" sort="Granell, Raquel" uniqKey="Granell R" first="Raquel" last="Granell">Raquel Granell</name><affiliation><nlm:aff id="A71">School of Social and Community Medicine, University of Bristol, Bristol, UK</nlm:aff></affiliation></author><author><name sortKey="Gu, Xiangjun" sort="Gu, Xiangjun" uniqKey="Gu X" first="Xiangjun" last="Gu">Xiangjun Gu</name><affiliation><nlm:aff id="A20">Brown Foundation Institute of Molecular Medicine, University of Texas at Houston, Houston, Texas, USA</nlm:aff></affiliation></author><author><name sortKey="Hankinson, John L" sort="Hankinson, John L" uniqKey="Hankinson J" first="John L" last="Hankinson">John L. Hankinson</name><affiliation><nlm:aff id="A72">Hankinson Consulting, Inc, Athens, Georgia, USA</nlm:aff></affiliation></author><author><name sortKey="Hardy, Rebecca" sort="Hardy, Rebecca" uniqKey="Hardy R" first="Rebecca" last="Hardy">Rebecca Hardy</name><affiliation><nlm:aff id="A70">MRC Unit for Lifelong Health and Ageing, London, UK</nlm:aff></affiliation></author><author><name sortKey="Harris, Sarah E" sort="Harris, Sarah E" uniqKey="Harris S" first="Sarah E" last="Harris">Sarah E. Harris</name><affiliation><nlm:aff id="A24">Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A73">Medical Genetics Section, The University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Henderson, John" sort="Henderson, John" uniqKey="Henderson J" first="John" last="Henderson">John Henderson</name><affiliation><nlm:aff id="A71">School of Social and Community Medicine, University of Bristol, Bristol, UK</nlm:aff></affiliation></author><author><name sortKey="Henry, Amanda" sort="Henry, Amanda" uniqKey="Henry A" first="Amanda" last="Henry">Amanda Henry</name><affiliation><nlm:aff id="A7">Division of Therapeutics and Molecular Medicine, Nottingham Respiratory Biomedical Research Unit, University Hospital of Nottingham, Nottingham, London, UK</nlm:aff></affiliation></author><author><name sortKey="Hingorani, Aroon D" sort="Hingorani, Aroon D" uniqKey="Hingorani A" first="Aroon D" last="Hingorani">Aroon D. Hingorani</name><affiliation><nlm:aff id="A74">Department of Epidemiology and Public Health, University College London, London, UK</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="A3">Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A75">Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Holt, Patrick G" sort="Holt, Patrick G" uniqKey="Holt P" first="Patrick G" last="Holt">Patrick G. Holt</name><affiliation><nlm:aff id="A76">Telethon Institute for Child Health Research and Centre for Child Health Research, The University of Western Australia, Perth, Western Australia, Australia</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="A48">Busselton Population Medical Research Foundation, Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A59">PathWest Laboratory Medicine of Western Australia, Queen Elizabeth II Medical Centre, Nedlands, Western Australia, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A77">School of Pathology and Laboratory Medicine, The University of Western Australia, Nedlands, Western Australia, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A78">School of Population Health, University of Western Australia, Nedlands, Western Australia, Australia</nlm:aff></affiliation></author><author><name sortKey="Hunter, Michael L" sort="Hunter, Michael L" uniqKey="Hunter M" first="Michael L" last="Hunter">Michael L. Hunter</name><affiliation><nlm:aff id="A48">Busselton Population Medical Research Foundation, Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A78">School of Population Health, University of Western Australia, Nedlands, Western Australia, Australia</nlm:aff></affiliation></author><author><name sortKey="Imboden, Medea" sort="Imboden, Medea" uniqKey="Imboden M" first="Medea" last="Imboden">Medea Imboden</name><affiliation><nlm:aff id="A65">Chronic Disease Epidemiology, Swiss Tropical and Public Health (TPH) Institute, Basel, Switzerland</nlm:aff></affiliation><affiliation><nlm:aff id="A66">University of Basel, Switzerland</nlm:aff></affiliation></author><author><name sortKey="Jameson, Karen A" sort="Jameson, Karen A" uniqKey="Jameson K" first="Karen A" last="Jameson">Karen A. Jameson</name><affiliation><nlm:aff id="A64">MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK</nlm:aff></affiliation></author><author><name sortKey="Kerr, Shona M" sort="Kerr, Shona M" uniqKey="Kerr S" first="Shona M" last="Kerr">Shona M. Kerr</name><affiliation><nlm:aff id="A79">Molecular Medicine Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Kolcic, Ivana" sort="Kolcic, Ivana" uniqKey="Kolcic I" first="Ivana" last="Kolcic">Ivana Kolcic</name><affiliation><nlm:aff id="A60">Faculty of Medicine, University of Split, Croatia, Split, Croatia</nlm:aff></affiliation></author><author><name sortKey="Kronenberg, Florian" sort="Kronenberg, Florian" uniqKey="Kronenberg F" first="Florian" last="Kronenberg">Florian Kronenberg</name><affiliation><nlm:aff id="A80">Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria</nlm:aff></affiliation></author><author><name sortKey="Liu, Jason Z" sort="Liu, Jason Z" uniqKey="Liu J" first="Jason Z" last="Liu">Jason Z. Liu</name><affiliation><nlm:aff id="A81">Department of Statistics, University of Oxford, Oxford, UK</nlm:aff></affiliation></author><author><name sortKey="Marchini, Jonathan" sort="Marchini, Jonathan" uniqKey="Marchini J" first="Jonathan" last="Marchini">Jonathan Marchini</name><affiliation><nlm:aff id="A81">Department of Statistics, University of Oxford, Oxford, UK</nlm:aff></affiliation></author><author><name sortKey="Mckeever, Tricia" sort="Mckeever, Tricia" uniqKey="Mckeever T" first="Tricia" last="Mckeever">Tricia Mckeever</name><affiliation><nlm:aff id="A62">Division of Epidemiology and Public Health, School of Community Health Sciences and Nottingham Respiratory Biomedical Research Unit, University of Nottingham, Nottingham, UK</nlm:aff></affiliation></author><author><name sortKey="Morris, Andrew D" sort="Morris, Andrew D" uniqKey="Morris A" first="Andrew D" last="Morris">Andrew D. Morris</name><affiliation><nlm:aff id="A82">Medical Research Institute, The University of Dundee, Dundee, UK</nlm:aff></affiliation></author><author><name sortKey="Olin, Anna Carin" sort="Olin, Anna Carin" uniqKey="Olin A" first="Anna-Carin" last="Olin">Anna-Carin Olin</name><affiliation><nlm:aff id="A61">Occupational and Environmental Medicine, Department of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden</nlm:aff></affiliation></author><author><name sortKey="Porteous, David J" sort="Porteous, David J" uniqKey="Porteous D" first="David J" last="Porteous">David J. Porteous</name><affiliation><nlm:aff id="A79">Molecular Medicine Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Postma, Dirkje S" sort="Postma, Dirkje S" uniqKey="Postma D" first="Dirkje S" last="Postma">Dirkje S. Postma</name><affiliation><nlm:aff id="A83">Department of Pulmonology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Rich, Stephen S" sort="Rich, Stephen S" uniqKey="Rich S" first="Stephen S" last="Rich">Stephen S. Rich</name><affiliation><nlm:aff id="A22">Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, USA</nlm:aff></affiliation></author><author><name sortKey="Ring, Susan M" sort="Ring, Susan M" uniqKey="Ring S" first="Susan M" last="Ring">Susan M. Ring</name><affiliation><nlm:aff id="A71">School of Social and Community Medicine, University of Bristol, Bristol, UK</nlm:aff></affiliation></author><author><name sortKey="Rivadeneira, Fernando" sort="Rivadeneira, Fernando" uniqKey="Rivadeneira F" first="Fernando" last="Rivadeneira">Fernando Rivadeneira</name><affiliation><nlm:aff id="A3">Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A84">Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A75">Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Rochat, Thierry" sort="Rochat, Thierry" uniqKey="Rochat T" first="Thierry" last="Rochat">Thierry Rochat</name><affiliation><nlm:aff id="A85">Division of Pulmonary Medicine, University Hospitals of Geneva, Geneva, Switzerland</nlm:aff></affiliation></author><author><name sortKey="Sayer, Avan Aihie" sort="Sayer, Avan Aihie" uniqKey="Sayer A" first="Avan Aihie" last="Sayer">Avan Aihie Sayer</name><affiliation><nlm:aff id="A64">MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK</nlm:aff></affiliation></author><author><name sortKey="Sayers, Ian" sort="Sayers, Ian" uniqKey="Sayers I" first="Ian" last="Sayers">Ian Sayers</name><affiliation><nlm:aff id="A7">Division of Therapeutics and Molecular Medicine, Nottingham Respiratory Biomedical Research Unit, University Hospital of Nottingham, Nottingham, London, UK</nlm:aff></affiliation></author><author><name sortKey="Sly, Peter D" sort="Sly, Peter D" uniqKey="Sly P" first="Peter D" last="Sly">Peter D. Sly</name><affiliation><nlm:aff id="A76">Telethon Institute for Child Health Research and Centre for Child Health Research, The University of Western Australia, Perth, Western Australia, Australia</nlm:aff></affiliation></author><author><name sortKey="Smith, George Davey" sort="Smith, George Davey" uniqKey="Smith G" first="George Davey" last="Smith">George Davey Smith</name><affiliation><nlm:aff id="A17">MRC Centre for Causal Analyses in Translational Epidemiology, School of Social and Community Medicine, University of Bristol, Bristol, UK</nlm:aff></affiliation></author><author><name sortKey="Sood, Akshay" sort="Sood, Akshay" uniqKey="Sood A" first="Akshay" last="Sood">Akshay Sood</name><affiliation><nlm:aff id="A86">Department of Medicine, University of New Mexico, Albuquerque, New Mexico, USA</nlm:aff></affiliation></author><author><name sortKey="Starr, John M" sort="Starr, John M" uniqKey="Starr J" first="John M" last="Starr">John M. Starr</name><affiliation><nlm:aff id="A24">Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A87">Geriatric Medicine Unit, The University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Uitterlinden, Andre G" sort="Uitterlinden, Andre G" uniqKey="Uitterlinden A" first="André G" last="Uitterlinden">André G. Uitterlinden</name><affiliation><nlm:aff id="A3">Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A84">Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A75">Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Vonk, Judith M" sort="Vonk, Judith M" uniqKey="Vonk J" first="Judith M" last="Vonk">Judith M. Vonk</name><affiliation><nlm:aff id="A88">Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Wannamethee, S Goya" sort="Wannamethee, S Goya" uniqKey="Wannamethee S" first="S Goya" last="Wannamethee">S Goya Wannamethee</name><affiliation><nlm:aff id="A89">Department of Primary Care and Population Health, University College London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Whincup, Peter H" sort="Whincup, Peter H" uniqKey="Whincup P" first="Peter H" last="Whincup">Peter H. Whincup</name><affiliation><nlm:aff id="A90">Division of Population Health Sciences and Education, St George’s University of London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Wijmenga, Cisca" sort="Wijmenga, Cisca" uniqKey="Wijmenga C" first="Cisca" last="Wijmenga">Cisca Wijmenga</name><affiliation><nlm:aff id="A91">Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Williams, O Dale" sort="Williams, O Dale" uniqKey="Williams O" first="O Dale" last="Williams">O Dale Williams</name><affiliation><nlm:aff id="A92">Division of Preventive Medicine, University of Alabama at Birmingham, Birmingham, USA</nlm:aff></affiliation></author><author><name sortKey="Wong, Andrew" sort="Wong, Andrew" uniqKey="Wong A" first="Andrew" last="Wong">Andrew Wong</name><affiliation><nlm:aff id="A70">MRC Unit for Lifelong Health and Ageing, London, UK</nlm:aff></affiliation></author><author><name sortKey="Mangino, Massimo" sort="Mangino, Massimo" uniqKey="Mangino M" first="Massimo" last="Mangino">Massimo Mangino</name><affiliation><nlm:aff id="A9">Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Marciante, Kristin D" sort="Marciante, Kristin D" uniqKey="Marciante K" first="Kristin D" last="Marciante">Kristin D. Marciante</name><affiliation><nlm:aff id="A6">Department of Medicine, University of Washington, Seattle, Washington, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A41">Cardiovascular Health Research Unit, University of Washington, Seattle, Washington, USA</nlm:aff></affiliation></author><author><name sortKey="Mcardle, Wendy L" sort="Mcardle, Wendy L" uniqKey="Mcardle W" first="Wendy L" last="Mcardle">Wendy L. Mcardle</name><affiliation><nlm:aff id="A71">School of Social and Community Medicine, University of Bristol, Bristol, UK</nlm:aff></affiliation></author><author><name sortKey="Meibohm, Bernd" sort="Meibohm, Bernd" uniqKey="Meibohm B" first="Bernd" last="Meibohm">Bernd Meibohm</name><affiliation><nlm:aff id="A93">College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee, USA</nlm:aff></affiliation></author><author><name sortKey="Morrison, Alanna C" sort="Morrison, Alanna C" uniqKey="Morrison A" first="Alanna C" last="Morrison">Alanna C. Morrison</name><affiliation><nlm:aff id="A21">Human Genetics Center, School of Public Health, University of Texas at Houston, Houston, Texas, USA</nlm:aff></affiliation></author><author><name sortKey="North, Kari E" sort="North, Kari E" uniqKey="North K" first="Kari E" last="North">Kari E. North</name><affiliation><nlm:aff id="A33">Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, USA</nlm:aff></affiliation></author><author><name sortKey="Omenaas, Ernst" sort="Omenaas, Ernst" uniqKey="Omenaas E" first="Ernst" last="Omenaas">Ernst Omenaas</name><affiliation><nlm:aff id="A94">Centre for Clinical Research, Haukeland University Hospital, Bergen, Norway</nlm:aff></affiliation></author><author><name sortKey="Palmer, Lyle J" sort="Palmer, Lyle J" uniqKey="Palmer L" first="Lyle J" last="Palmer">Lyle J. Palmer</name><affiliation><nlm:aff id="A18">Genetic Epidemiology and Biostatistics Platform, Ontario Institute for Cancer Research, Toronto, Ontario, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="A19">Prosserman Centre for Health Research, Samuel Lunenfeld Research Institute, Toronto, Ontario, Canada</nlm:aff></affiliation></author><author><name sortKey="Pietil Inen, Kirsi H" sort="Pietil Inen, Kirsi H" uniqKey="Pietil Inen K" first="Kirsi H" last="Pietil Inen">Kirsi H. Pietil Inen</name><affiliation><nlm:aff id="A95">Obesity Research Unit, Department of Medicine, Division of Internal Medicine, Helsinki University Central Hospital, Helsinki, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A96">Hjelt Institute, Department of Public Health, University of Helsinki, Helsinki, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A97">Institute for Molecular Medicine, University of Helsinki, Helsinki, Finland</nlm:aff></affiliation></author><author><name sortKey="Pin, Isabelle" sort="Pin, Isabelle" uniqKey="Pin I" first="Isabelle" last="Pin">Isabelle Pin</name><affiliation><nlm:aff id="A98">Pédiatrie, Centre Hospitalier Universitaire (CHU), Grenoble, France</nlm:aff></affiliation><affiliation><nlm:aff id="A99">Inserm U823, Centre de Recherche Albert Bonniot, Grenoble, France</nlm:aff></affiliation><affiliation><nlm:aff id="A100">Université Joseph Fourier, Grenoble, France</nlm:aff></affiliation></author><author><name sortKey="Polasek, Ozren" sort="Polasek, Ozren" uniqKey="Polasek O" first="Ozren" last="Polašek">Ozren Polašek</name><affiliation><nlm:aff id="A60">Faculty of Medicine, University of Split, Croatia, Split, Croatia</nlm:aff></affiliation><affiliation><nlm:aff id="A101">Gen-Info Ltd, Zagreb, Croatia</nlm:aff></affiliation></author><author><name sortKey="Pouta, Anneli" sort="Pouta, Anneli" uniqKey="Pouta A" first="Anneli" last="Pouta">Anneli Pouta</name><affiliation><nlm:aff id="A102">Department of Children, Young People and Families, National Institute for Health and Welfare, Oulu, Finland</nlm:aff></affiliation></author><author><name sortKey="Psaty, Bruce M" sort="Psaty, Bruce M" uniqKey="Psaty B" first="Bruce M" last="Psaty">Bruce M. Psaty</name><affiliation><nlm:aff id="A6">Department of Medicine, University of Washington, Seattle, Washington, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A41">Cardiovascular Health Research Unit, University of Washington, Seattle, Washington, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A42">Department of Epidemiology, University of Washington, Seattle, Washington, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A43">Group Health Research Institute, Group Health Cooperative, Seattle, Washington, USA</nlm:aff></affiliation></author><author><name sortKey="Hartikainen, Anna Liisa" sort="Hartikainen, Anna Liisa" uniqKey="Hartikainen A" first="Anna-Liisa" last="Hartikainen">Anna-Liisa Hartikainen</name><affiliation><nlm:aff id="A103">Institute of Clinical Medicine, University of Oulu, Oulu, Finland</nlm:aff></affiliation></author><author><name sortKey="Rantanen, Taina" sort="Rantanen, Taina" uniqKey="Rantanen T" first="Taina" last="Rantanen">Taina Rantanen</name><affiliation><nlm:aff id="A104"> Gerontology Research Centre, Department of Health Sciences, University of Jyväskylä, Jyväskylä, Finland</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="A97">Institute for Molecular Medicine, University of Helsinki, Helsinki, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A105">Public Health Genomics Unit, Department Of Chronic Disease Prevention, The National Institute for Health and Welfare, Helsinki, Finland</nlm:aff></affiliation></author><author><name sortKey="Rotter, Jerome I" sort="Rotter, Jerome I" uniqKey="Rotter J" first="Jerome I" last="Rotter">Jerome I. Rotter</name><affiliation><nlm:aff id="A106">Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA</nlm:aff></affiliation></author><author><name sortKey="Rudan, Igor" sort="Rudan, Igor" uniqKey="Rudan I" first="Igor" last="Rudan">Igor Rudan</name><affiliation><nlm:aff id="A31">Centre for Population Health Sciences, The University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A35">Croatian Centre for Global Health, The University of Split Medical School, Split, Croatia</nlm:aff></affiliation><affiliation><nlm:aff id="A101">Gen-Info Ltd, Zagreb, Croatia</nlm:aff></affiliation></author><author><name sortKey="Rudnicka, Alicja R" sort="Rudnicka, Alicja R" uniqKey="Rudnicka A" first="Alicja R" last="Rudnicka">Alicja R. Rudnicka</name><affiliation><nlm:aff id="A90">Division of Population Health Sciences and Education, St George’s University of London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Schulz, Holger" sort="Schulz, Holger" uniqKey="Schulz H" first="Holger" last="Schulz">Holger Schulz</name><affiliation><nlm:aff id="A107">Institute of Epidemiology I, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany</nlm:aff></affiliation></author><author><name sortKey="Shin, So Youn" sort="Shin, So Youn" uniqKey="Shin S" first="So-Youn" last="Shin">So-Youn Shin</name><affiliation><nlm:aff id="A29">Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Spector, Tim D" sort="Spector, Tim D" uniqKey="Spector T" first="Tim D" last="Spector">Tim D. Spector</name><affiliation><nlm:aff id="A9">Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Surakka, Ida" sort="Surakka, Ida" uniqKey="Surakka I" first="Ida" last="Surakka">Ida Surakka</name><affiliation><nlm:aff id="A97">Institute for Molecular Medicine, University of Helsinki, Helsinki, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A105">Public Health Genomics Unit, Department Of Chronic Disease Prevention, The National Institute for Health and Welfare, Helsinki, Finland</nlm:aff></affiliation></author><author><name sortKey="Vitart, Veronique" sort="Vitart, Veronique" uniqKey="Vitart V" first="Veronique" last="Vitart">Veronique Vitart</name><affiliation><nlm:aff id="A14">MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Volzke, Henry" sort="Volzke, Henry" uniqKey="Volzke H" first="Henry" last="Völzke">Henry Völzke</name><affiliation><nlm:aff id="A108">Institute for Community Medicine, Study of Health In Pomerania (SHIP)/Clinical Epidemiological Research, University of Greifswald, Greifswald, Germany</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="A11">Medical Research Council (MRC) Epidemiology Unit, Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Warrington, Nicole M" sort="Warrington, Nicole M" uniqKey="Warrington N" first="Nicole M" last="Warrington">Nicole M. Warrington</name><affiliation><nlm:aff id="A56">School of Women’s and Infants’ Health, The University of Western Australia, Perth, Western Australia, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A19">Prosserman Centre for Health Research, Samuel Lunenfeld Research Institute, Toronto, Ontario, Canada</nlm:aff></affiliation></author><author><name sortKey="Wichmann, H Erich" sort="Wichmann, H Erich" uniqKey="Wichmann H" first="H-Erich" last="Wichmann">H-Erich Wichmann</name><affiliation><nlm:aff id="A107">Institute of Epidemiology I, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A109">Institute of Medical Informatics, Biometry and Epidemiology, Chair of Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A110">Klinikum Grosshadern, Munich, Germany</nlm:aff></affiliation></author><author><name sortKey="Wild, Sarah H" sort="Wild, Sarah H" uniqKey="Wild S" first="Sarah H" last="Wild">Sarah H. Wild</name><affiliation><nlm:aff id="A31">Centre for Population Health Sciences, The University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Wilk, Jemma B" sort="Wilk, Jemma B" uniqKey="Wilk J" first="Jemma B" last="Wilk">Jemma B. Wilk</name><affiliation><nlm:aff id="A111">Division of Aging, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Wjst, Matthias" sort="Wjst, Matthias" uniqKey="Wjst M" first="Matthias" last="Wjst">Matthias Wjst</name><affiliation><nlm:aff id="A112">Institute of Lung Biology and Disease, Comprehensive Pneumology Center, Helmholtz Zentrum München, Neuherberg, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A113">Institute for Medical Statistics and Epidemiology (IMSE), Technical University Munich, Munich, Germany</nlm:aff></affiliation></author><author><name sortKey="Wright, Alan F" sort="Wright, Alan F" uniqKey="Wright A" first="Alan F" last="Wright">Alan F. Wright</name><affiliation><nlm:aff id="A14">MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Zgaga, Lina" sort="Zgaga, Lina" uniqKey="Zgaga L" first="Lina" last="Zgaga">Lina Zgaga</name><affiliation><nlm:aff id="A114">Andrija Stampar School of Public Health, Faculty of Medicine, University of Zagreb, Zagreb, Croatia</nlm:aff></affiliation><affiliation><nlm:aff id="A31">Centre for Population Health Sciences, The University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Zemunik, Tatijana" sort="Zemunik, Tatijana" uniqKey="Zemunik T" first="Tatijana" last="Zemunik">Tatijana Zemunik</name><affiliation><nlm:aff id="A60">Faculty of Medicine, University of Split, Croatia, Split, Croatia</nlm:aff></affiliation></author><author><name sortKey="Pennell, Craig E" sort="Pennell, Craig E" uniqKey="Pennell C" first="Craig E" last="Pennell">Craig E. Pennell</name><affiliation><nlm:aff id="A56">School of Women’s and Infants’ Health, The University of Western Australia, Perth, Western Australia, Australia</nlm:aff></affiliation></author><author><name sortKey="Nyberg, Fredrik" sort="Nyberg, Fredrik" uniqKey="Nyberg F" first="Fredrik" last="Nyberg">Fredrik Nyberg</name><affiliation><nlm:aff id="A61">Occupational and Environmental Medicine, Department of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden</nlm:aff></affiliation><affiliation><nlm:aff id="A115">AstraZeneca Research and Development, Mölndal, Sweden</nlm:aff></affiliation></author><author><name sortKey="Kuh, Diana" sort="Kuh, Diana" uniqKey="Kuh D" first="Diana" last="Kuh">Diana Kuh</name><affiliation><nlm:aff id="A70">MRC Unit for Lifelong Health and Ageing, London, UK</nlm:aff></affiliation></author><author><name sortKey="Holloway, John W" sort="Holloway, John W" uniqKey="Holloway J" first="John W" last="Holloway">John W. Holloway</name><affiliation><nlm:aff id="A116">Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A117">Infection, Inflammation and Immunity, Faculty of Medicine, University of Southampton, Southampton, UK</nlm:aff></affiliation></author><author><name sortKey="Boezen, H Marike" sort="Boezen, H Marike" uniqKey="Boezen H" first="H Marike" last="Boezen">H Marike Boezen</name><affiliation><nlm:aff id="A88">Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Lawlor, Debbie A" sort="Lawlor, Debbie A" uniqKey="Lawlor D" first="Debbie A" last="Lawlor">Debbie A. Lawlor</name><affiliation><nlm:aff id="A17">MRC Centre for Causal Analyses in Translational Epidemiology, School of Social and Community Medicine, University of Bristol, Bristol, UK</nlm:aff></affiliation></author><author><name sortKey="Morris, Richard W" sort="Morris, Richard W" uniqKey="Morris R" first="Richard W" last="Morris">Richard W. Morris</name><affiliation><nlm:aff id="A89">Department of Primary Care and Population Health, University College London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Probst Hensch, Nicole" sort="Probst Hensch, Nicole" uniqKey="Probst Hensch N" first="Nicole" last="Probst-Hensch">Nicole Probst-Hensch</name><affiliation><nlm:aff id="A65">Chronic Disease Epidemiology, Swiss Tropical and Public Health (TPH) Institute, Basel, Switzerland</nlm:aff></affiliation><affiliation><nlm:aff id="A66">University of Basel, Switzerland</nlm:aff></affiliation></author><author><name sortKey="Kaprio, Jaakko" sort="Kaprio, Jaakko" uniqKey="Kaprio J" first="Jaakko" last="Kaprio">Jaakko Kaprio</name><affiliation><nlm:aff id="A44">National Institute for Health and Welfare, Helsinki, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A96">Hjelt Institute, Department of Public Health, University of Helsinki, Helsinki, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A97">Institute for Molecular Medicine, University of Helsinki, Helsinki, Finland</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="A31">Centre for Population Health Sciences, The University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Hayward, Caroline" sort="Hayward, Caroline" uniqKey="Hayward C" first="Caroline" last="Hayward">Caroline Hayward</name><affiliation><nlm:aff id="A14">MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="K Honen, Mika" sort="K Honen, Mika" uniqKey="K Honen M" first="Mika" last="K Hönen">Mika K Hönen</name><affiliation><nlm:aff id="A118">Department of Clinical Physiology, University of Tampere and Tampere University Hospital, Tampere, Finland</nlm:aff></affiliation></author><author><name sortKey="Heinrich, Joachim" sort="Heinrich, Joachim" uniqKey="Heinrich J" first="Joachim" last="Heinrich">Joachim Heinrich</name><affiliation><nlm:aff id="A107">Institute of Epidemiology I, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany</nlm:aff></affiliation></author><author><name sortKey="Musk, Arthur W" sort="Musk, Arthur W" uniqKey="Musk A" first="Arthur W" last="Musk">Arthur W. Musk</name><affiliation><nlm:aff id="A48">Busselton Population Medical Research Foundation, Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A119">Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A78">School of Population Health, University of Western Australia, Nedlands, Western Australia, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A47">The School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia</nlm:aff></affiliation></author><author><name sortKey="Jarvis, Deborah L" sort="Jarvis, Deborah L" uniqKey="Jarvis D" first="Deborah L" last="Jarvis">Deborah L. Jarvis</name><affiliation><nlm:aff id="A38"> Respiratory Epidemiology and Public Health, Imperial College London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A120">MRC Health Protection Agency (HPA) Centre for Environment and Health, Imperial College London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Gl Ser, Sven" sort="Gl Ser, Sven" uniqKey="Gl Ser S" first="Sven" last="Gl Ser">Sven Gl Ser</name><affiliation><nlm:aff id="A121">University Hospital Greifswald, Department of Internal Medicine B, Greifswald, Germany</nlm:aff></affiliation></author><author><name sortKey="J Rvelin, Marjo Riitta" sort="J Rvelin, Marjo Riitta" uniqKey="J Rvelin M" first="Marjo-Riitta" last="J Rvelin">Marjo-Riitta J Rvelin</name><affiliation><nlm:aff id="A39">Department of Epidemiology and Biostatistics, Imperial College London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A122">Institute of Health Sciences, University of Oulu, Oulu, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A123">Biocenter Oulu, University of Oulu, Oulu, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A102">Department of Children, Young People and Families, National Institute for Health and Welfare, Oulu, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A120">MRC Health Protection Agency (HPA) Centre for Environment and Health, Imperial College London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Stricker, Bruno H Ch" sort="Stricker, Bruno H Ch" uniqKey="Stricker B" first="Bruno H Ch" last="Stricker">Bruno H Ch Stricker</name><affiliation><nlm:aff id="A3">Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Inspectorate of Healthcare, The Hague, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A84">Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A75">Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A124">Department of Medical Informatics, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Elliott, Paul" sort="Elliott, Paul" uniqKey="Elliott P" first="Paul" last="Elliott">Paul Elliott</name><affiliation><nlm:aff id="A120">MRC Health Protection Agency (HPA) Centre for Environment and Health, Imperial College London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A39">Department of Epidemiology and Biostatistics, Imperial College London, London, UK</nlm:aff></affiliation></author><author><name sortKey="O Onnor, George T" sort="O Onnor, George T" uniqKey="O Onnor G" first="George T" last="O Onnor">George T. O Onnor</name><affiliation><nlm:aff id="A125">Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A126">The National Heart, Lung and Blood Institute’s Framingham Heart Study, Framingham, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Strachan, David P" sort="Strachan, David P" uniqKey="Strachan D" first="David P" last="Strachan">David P. Strachan</name><affiliation><nlm:aff id="A90">Division of Population Health Sciences and Education, St George’s University of London, London, UK</nlm:aff></affiliation></author><author><name sortKey="London, Stephanie J" sort="London, Stephanie J" uniqKey="London S" first="Stephanie J" last="London">Stephanie J. London</name><affiliation><nlm:aff id="A36">Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA</nlm:aff></affiliation></author><author><name sortKey="Hall, Ian P" sort="Hall, Ian P" uniqKey="Hall I" first="Ian P" last="Hall">Ian P. Hall</name><affiliation><nlm:aff id="A7">Division of Therapeutics and Molecular Medicine, Nottingham Respiratory Biomedical Research Unit, University Hospital of Nottingham, Nottingham, London, UK</nlm:aff></affiliation></author><author><name sortKey="Gudnason, Vilmundur" sort="Gudnason, Vilmundur" uniqKey="Gudnason V" first="Vilmundur" last="Gudnason">Vilmundur Gudnason</name><affiliation><nlm:aff id="A12">Icelandic Heart Association, Kopavogur, Iceland</nlm:aff></affiliation><affiliation><nlm:aff id="A13">University of Iceland, Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Tobin, Martin D" sort="Tobin, Martin D" uniqKey="Tobin M" first="Martin D" last="Tobin">Martin D. Tobin</name><affiliation><nlm:aff id="A1">Department of Health Sciences, University of Leicester, Leicester, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Genetics, University of Leicester, Leicester, 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="2011">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P3">Pulmonary function measures reflect respiratory health and predict mortality, and are used in the diagnosis of chronic obstructive pulmonary disease (COPD). We tested genome-wide association with the forced expiratory volume in 1 second (FEV<sub>1</sub>) and the ratio of FEV<sub>1</sub> to forced vital capacity (FVC) in 48,201 individuals of European ancestry, with follow-up of top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined <italic>P</italic><5×10<sup>−8</sup>) with pulmonary function, in or near <italic>MFAP2, TGFB2, HDAC4, RARB, MECOM</italic> (<italic>EVI1</italic>), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1, and <italic>KCNE2</italic>. Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Wilk, Jb" uniqKey="Wilk J">JB Wilk</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hole, Dj" uniqKey="Hole D">DJ Hole</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Strachan, Dp" uniqKey="Strachan D">DP Strachan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Young, Rp" uniqKey="Young R">RP Young</name></author><author><name sortKey="Hopkins, R" uniqKey="Hopkins R">R Hopkins</name></author><author><name sortKey="Eaton, Te" uniqKey="Eaton T">TE Eaton</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lopez, Ad" uniqKey="Lopez A">AD Lopez</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mathers, Cd" uniqKey="Mathers C">CD Mathers</name></author><author><name sortKey="Loncar, D" uniqKey="Loncar D">D Loncar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rabe, Kf" uniqKey="Rabe K">KF Rabe</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hancock, Db" uniqKey="Hancock D">DB Hancock</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Repapi, E" uniqKey="Repapi E">E Repapi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pillai, Sg" uniqKey="Pillai S">SG Pillai</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wilk, Jb" uniqKey="Wilk J">JB Wilk</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yang, J" uniqKey="Yang J">J 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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">21946350</article-id><article-id pub-id-type="pmc">3267376</article-id><article-id pub-id-type="doi">10.1038/ng.941</article-id><article-id pub-id-type="manuscript">NIHMS335195</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Genome-wide association and large scale follow-up identifies 16 new loci influencing lung function</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Artigas</surname><given-names>María Soler</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref><xref ref-type="author-notes" rid="FN2">128</xref></contrib><contrib 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rid="A88">88</xref></contrib><contrib contrib-type="author"><name><surname>Lawlor</surname><given-names>Debbie A</given-names></name><xref ref-type="aff" rid="A17">17</xref></contrib><contrib contrib-type="author"><name><surname>Morris</surname><given-names>Richard W</given-names></name><xref ref-type="aff" rid="A89">89</xref></contrib><contrib contrib-type="author"><name><surname>Probst-Hensch</surname><given-names>Nicole</given-names></name><xref ref-type="aff" rid="A65">65</xref><xref ref-type="aff" rid="A66">66</xref></contrib><contrib contrib-type="author"><collab>The International Lung Cancer Consortium</collab><xref ref-type="author-notes" rid="FN1">127</xref></contrib><contrib contrib-type="author"><collab>GIANT consortium</collab><xref ref-type="author-notes" rid="FN1">127</xref></contrib><contrib contrib-type="author"><name><surname>Kaprio</surname><given-names>Jaakko</given-names></name><xref ref-type="aff" rid="A44">44</xref><xref ref-type="aff" rid="A96">96</xref><xref 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ref-type="author-notes" rid="FN2">128</xref></contrib><contrib contrib-type="author"><name><surname>Elliott</surname><given-names>Paul</given-names></name><xref ref-type="aff" rid="A120">120</xref><xref ref-type="aff" rid="A39">39</xref><xref ref-type="author-notes" rid="FN2">128</xref></contrib><contrib contrib-type="author"><name><surname>O’Connor</surname><given-names>George T</given-names></name><xref ref-type="aff" rid="A125">125</xref><xref ref-type="aff" rid="A126">126</xref><xref ref-type="author-notes" rid="FN2">128</xref></contrib><contrib contrib-type="author"><name><surname>Strachan</surname><given-names>David P</given-names></name><xref ref-type="aff" rid="A90">90</xref><xref ref-type="author-notes" rid="FN2">128</xref></contrib><contrib contrib-type="author"><name><surname>London</surname><given-names>Stephanie J</given-names></name><xref ref-type="aff" rid="A36">36</xref><xref ref-type="author-notes" rid="FN2">128</xref></contrib><contrib contrib-type="author"><name><surname>Hall</surname><given-names>Ian P</given-names></name><xref ref-type="aff" rid="A7">7</xref><xref ref-type="author-notes" rid="FN2">128</xref></contrib><contrib contrib-type="author"><name><surname>Gudnason</surname><given-names>Vilmundur</given-names></name><xref ref-type="aff" rid="A12">12</xref><xref ref-type="aff" rid="A13">13</xref><xref ref-type="author-notes" rid="FN2">128</xref></contrib><contrib contrib-type="author"><name><surname>Tobin</surname><given-names>Martin D</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref><xref ref-type="author-notes" rid="FN2">128</xref></contrib></contrib-group><aff id="A1"><label>1</label>Department of Health Sciences, University of Leicester, Leicester, UK</aff><aff id="A2"><label>2</label>Department of Genetics, University of Leicester, Leicester, UK</aff><aff id="A3"><label>3</label>Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands</aff><aff id="A4"><label>4</label>Inspectorate of Healthcare, The Hague, The Netherlands</aff><aff id="A5"><label>5</label>Center for Lung Biology, University of Washington, Seattle, Washington, USA</aff><aff id="A6"><label>6</label>Department of Medicine, University of Washington, Seattle, Washington, USA</aff><aff id="A7"><label>7</label>Division of Therapeutics and Molecular Medicine, Nottingham Respiratory Biomedical Research Unit, University Hospital of Nottingham, Nottingham, London, UK</aff><aff id="A8"><label>8</label>Division of Nutritional Sciences, Cornell University Ithaca, New York, USA</aff><aff id="A9"><label>9</label>Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK</aff><aff id="A10"><label>10</label>Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, Newfoundland, Canada</aff><aff id="A11"><label>11</label>Medical Research Council (MRC) Epidemiology Unit, Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge, UK</aff><aff id="A12"><label>12</label>Icelandic Heart Association, Kopavogur, Iceland</aff><aff id="A13"><label>13</label>University of Iceland, Reykjavik, Iceland</aff><aff id="A14"><label>14</label>MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK</aff><aff id="A15"><label>15</label>Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany</aff><aff id="A16"><label>16</label>School of Medicine, University of St. Andrews, St. Andrews, Scotland, UK</aff><aff id="A17"><label>17</label>MRC Centre for Causal Analyses in Translational Epidemiology, School of Social and Community Medicine, University of Bristol, Bristol, UK</aff><aff id="A18"><label>18</label>Genetic Epidemiology and Biostatistics Platform, Ontario Institute for Cancer Research, Toronto, Ontario, Canada</aff><aff id="A19"><label>19</label>Prosserman Centre for Health Research, Samuel Lunenfeld Research Institute, Toronto, Ontario, Canada</aff><aff id="A20"><label>20</label>Brown Foundation Institute of Molecular Medicine, University of Texas at Houston, Houston, Texas, USA</aff><aff id="A21"><label>21</label>Human Genetics Center, School of Public Health, University of Texas at Houston, Houston, Texas, USA</aff><aff id="A22"><label>22</label>Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, USA</aff><aff id="A23"><label>23</label>Department of Public Health Sciences, Division of Biostatistics and Epidemiology, University of Virginia, Charlottesville, Virginia, USA</aff><aff id="A24"><label>24</label>Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, UK</aff><aff id="A25"><label>25</label>Department of Psychology, The University of Edinburgh, Edinburgh, UK</aff><aff id="A26"><label>26</label>Clinical Pharmacology and the Genome Centre, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK</aff><aff id="A27"><label>27</label>Department of Thoracic Surgery, Vanderbilt University, Nashville, Tennessee, USA</aff><aff id="A28"><label>28</label>Division of Epidemiology, Vanderbilt University, Nashville, Tennessee, USA</aff><aff id="A29"><label>29</label>Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge, UK</aff><aff id="A30"><label>30</label>University of Cambridge Metabolic Research Labs, Institute of Metabolic Science Addenbrooke’s Hospital, Cambridge, UK</aff><aff id="A31"><label>31</label>Centre for Population Health Sciences, The University of Edinburgh, Edinburgh, UK</aff><aff id="A32"><label>32</label>Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, USA</aff><aff id="A33"><label>33</label>Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, USA</aff><aff id="A34"><label>34</label>Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA</aff><aff id="A35"><label>35</label>Croatian Centre for Global Health, The University of Split Medical School, Split, Croatia</aff><aff id="A36"><label>36</label>Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA</aff><aff id="A37"><label>37</label>Behavioral Health Epidemiology Program, Research Triangle Institute International, Research Triangle Park, North Carolina, USA</aff><aff id="A38"><label>38</label> Respiratory Epidemiology and Public Health, Imperial College London, London, UK</aff><aff id="A39"><label>39</label>Department of Epidemiology and Biostatistics, Imperial College London, London, UK</aff><aff id="A40"><label>40</label>Department of Medical and Molecular Genetics, King’s College London, Guy’s Hospital, London, UK</aff><aff id="A41"><label>41</label>Cardiovascular Health Research Unit, University of Washington, Seattle, Washington, USA</aff><aff id="A42"><label>42</label>Department of Epidemiology, University of Washington, Seattle, Washington, USA</aff><aff id="A43"><label>43</label>Group Health Research Institute, Group Health Cooperative, Seattle, Washington, USA</aff><aff id="A44"><label>44</label>National Institute for Health and Welfare, Helsinki, Finland</aff><aff id="A45"><label>45</label>Interfaculty Institute for Genetics and Functional Genomics, Department of Functional Genomics, University of Greifswald, Greifswald, Germany</aff><aff id="A46"><label>46</label>Department of Pulmonary Physiology and Sleep Medicine/West Australian Sleep Disorders Research Institute, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia</aff><aff id="A47"><label>47</label>The School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia</aff><aff id="A48"><label>48</label>Busselton Population Medical Research Foundation, Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia</aff><aff id="A49"><label>49</label>Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, Ludwig-Maximilians-University, Munich, Germany</aff><aff id="A50"><label>50</label>Unit for Molecular Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany</aff><aff id="A51"><label>51</label>Department of Internal Medicine B, University Hospital Greifswald, Greifswald, Germany</aff><aff id="A52"><label>52</label>Sticht Center on Aging, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA</aff><aff id="A53"><label>53</label>Epidemiology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA</aff><aff id="A54"><label>54</label>Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA</aff><aff id="A55"><label>55</label>Department of Statistics, University of Auckland, Auckland, New Zealand</aff><aff id="A56"><label>56</label>School of Women’s and Infants’ Health, The University of Western Australia, Perth, Western Australia, Australia</aff><aff id="A57"><label>57</label>Department of Medicine, Columbia University Medical Center, New York, New York, USA</aff><aff id="A58"><label>58</label>Department of Surgery and Pathology, University of Western Australia, Nedlands, Western Australia, Australia</aff><aff id="A59"><label>59</label>PathWest Laboratory Medicine of Western Australia, Queen Elizabeth II Medical Centre, Nedlands, Western Australia, Australia</aff><aff id="A60"><label>60</label>Faculty of Medicine, University of Split, Croatia, Split, Croatia</aff><aff id="A61"><label>61</label>Occupational and Environmental Medicine, Department of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden</aff><aff id="A62"><label>62</label>Division of Epidemiology and Public Health, School of Community Health Sciences and Nottingham Respiratory Biomedical Research Unit, University of Nottingham, Nottingham, UK</aff><aff id="A63"><label>63</label>Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium</aff><aff id="A64"><label>64</label>MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK</aff><aff id="A65"><label>65</label>Chronic Disease Epidemiology, Swiss Tropical and Public Health (TPH) Institute, Basel, Switzerland</aff><aff id="A66"><label>66</label>University of Basel, Switzerland</aff><aff id="A67"><label>67</label>Non-Communicable Diseases Epidemiology Unit, Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK</aff><aff id="A68"><label>68</label>South Asia Centre for Chronic Disease, New Delhi, India</aff><aff id="A69"><label>69</label>Max Planck Institute for Psycholinguistics, Nijmegen, The Netherlands</aff><aff id="A70"><label>70</label>MRC Unit for Lifelong Health and Ageing, London, UK</aff><aff id="A71"><label>71</label>School of Social and Community Medicine, University of Bristol, Bristol, UK</aff><aff id="A72"><label>72</label>Hankinson Consulting, Inc, Athens, Georgia, USA</aff><aff id="A73"><label>73</label>Medical Genetics Section, The University of Edinburgh, Edinburgh, UK</aff><aff id="A74"><label>74</label>Department of Epidemiology and Public Health, University College London, London, UK</aff><aff id="A75"><label>75</label>Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), The Netherlands</aff><aff id="A76"><label>76</label>Telethon Institute for Child Health Research and Centre for Child Health Research, The University of Western Australia, Perth, Western Australia, Australia</aff><aff id="A77"><label>77</label>School of Pathology and Laboratory Medicine, The University of Western Australia, Nedlands, Western Australia, Australia</aff><aff id="A78"><label>78</label>School of Population Health, University of Western Australia, Nedlands, Western Australia, Australia</aff><aff id="A79"><label>79</label>Molecular Medicine Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK</aff><aff id="A80"><label>80</label>Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria</aff><aff id="A81"><label>81</label>Department of Statistics, University of Oxford, Oxford, UK</aff><aff id="A82"><label>82</label>Medical Research Institute, The University of Dundee, Dundee, UK</aff><aff id="A83"><label>83</label>Department of Pulmonology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands</aff><aff id="A84"><label>84</label>Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands</aff><aff id="A85"><label>85</label>Division of Pulmonary Medicine, University Hospitals of Geneva, Geneva, Switzerland</aff><aff id="A86"><label>86</label>Department of Medicine, University of New Mexico, Albuquerque, New Mexico, USA</aff><aff id="A87"><label>87</label>Geriatric Medicine Unit, The University of Edinburgh, Edinburgh, UK</aff><aff id="A88"><label>88</label>Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands</aff><aff id="A89"><label>89</label>Department of Primary Care and Population Health, University College London, London, UK</aff><aff id="A90"><label>90</label>Division of Population Health Sciences and Education, St George’s University of London, London, UK</aff><aff id="A91"><label>91</label>Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands</aff><aff id="A92"><label>92</label>Division of Preventive Medicine, University of Alabama at Birmingham, Birmingham, USA</aff><aff id="A93"><label>93</label>College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee, USA</aff><aff id="A94"><label>94</label>Centre for Clinical Research, Haukeland University Hospital, Bergen, Norway</aff><aff id="A95"><label>95</label>Obesity Research Unit, Department of Medicine, Division of Internal Medicine, Helsinki University Central Hospital, Helsinki, Finland</aff><aff id="A96"><label>96</label>Hjelt Institute, Department of Public Health, University of Helsinki, Helsinki, Finland</aff><aff id="A97"><label>97</label>Institute for Molecular Medicine, University of Helsinki, Helsinki, Finland</aff><aff id="A98"><label>98</label>Pédiatrie, Centre Hospitalier Universitaire (CHU), Grenoble, France</aff><aff id="A99"><label>99</label>Inserm U823, Centre de Recherche Albert Bonniot, Grenoble, France</aff><aff id="A100"><label>100</label>Université Joseph Fourier, Grenoble, France</aff><aff id="A101"><label>101</label>Gen-Info Ltd, Zagreb, Croatia</aff><aff id="A102"><label>102</label>Department of Children, Young People and Families, National Institute for Health and Welfare, Oulu, Finland</aff><aff id="A103"><label>103</label>Institute of Clinical Medicine, University of Oulu, Oulu, Finland</aff><aff id="A104"><label>104</label> Gerontology Research Centre, Department of Health Sciences, University of Jyväskylä, Jyväskylä, Finland</aff><aff id="A105"><label>105</label>Public Health Genomics Unit, Department Of Chronic Disease Prevention, The National Institute for Health and Welfare, Helsinki, Finland</aff><aff id="A106"><label>106</label>Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA</aff><aff id="A107"><label>107</label>Institute of Epidemiology I, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany</aff><aff id="A108"><label>108</label>Institute for Community Medicine, Study of Health In Pomerania (SHIP)/Clinical Epidemiological Research, University of Greifswald, Greifswald, Germany</aff><aff id="A109"><label>109</label>Institute of Medical Informatics, Biometry and Epidemiology, Chair of Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany</aff><aff id="A110"><label>110</label>Klinikum Grosshadern, Munich, Germany</aff><aff id="A111"><label>111</label>Division of Aging, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA</aff><aff id="A112"><label>112</label>Institute of Lung Biology and Disease, Comprehensive Pneumology Center, Helmholtz Zentrum München, Neuherberg, Germany</aff><aff id="A113"><label>113</label>Institute for Medical Statistics and Epidemiology (IMSE), Technical University Munich, Munich, Germany</aff><aff id="A114"><label>114</label>Andrija Stampar School of Public Health, Faculty of Medicine, University of Zagreb, Zagreb, Croatia</aff><aff id="A115"><label>115</label>AstraZeneca Research and Development, Mölndal, Sweden</aff><aff id="A116"><label>116</label>Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK</aff><aff id="A117"><label>117</label>Infection, Inflammation and Immunity, Faculty of Medicine, University of Southampton, Southampton, UK</aff><aff id="A118"><label>118</label>Department of Clinical Physiology, University of Tampere and Tampere University Hospital, Tampere, Finland</aff><aff id="A119"><label>119</label>Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia</aff><aff id="A120"><label>120</label>MRC Health Protection Agency (HPA) Centre for Environment and Health, Imperial College London, London, UK</aff><aff id="A121"><label>121</label>University Hospital Greifswald, Department of Internal Medicine B, Greifswald, Germany</aff><aff id="A122"><label>122</label>Institute of Health Sciences, University of Oulu, Oulu, Finland</aff><aff id="A123"><label>123</label>Biocenter Oulu, University of Oulu, Oulu, Finland</aff><aff id="A124"><label>124</label>Department of Medical Informatics, Erasmus Medical Center, Rotterdam, The Netherlands</aff><aff id="A125"><label>125</label>Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts, USA</aff><aff id="A126"><label>126</label>The National Heart, Lung and Blood Institute’s Framingham Heart Study, Framingham, Massachusetts, USA</aff><author-notes><fn id="FN1"><label>127</label><p id="P1">A full list of members is provided in the <xref ref-type="supplementary-material" rid="SD1">Supplementary Note</xref>.</p></fn><fn fn-type="equal" id="FN2"><label>128</label><p id="P2">These authors contributed equally to this work. Correspondence should be addressed to M.D.T. (<email>mt47@leicester.ac.uk</email>) or S.J.L. (<email>london2@niehs.nih.gov</email>).</p></fn></author-notes><pub-date pub-type="nihms-submitted"><day>10</day><month>11</month><year>2011</year></pub-date><pub-date pub-type="epub"><day>25</day><month>9</month><year>2011</year></pub-date><pub-date pub-type="collection"><month>11</month><year>2011</year></pub-date><pub-date pub-type="pmc-release"><day>01</day><month>5</month><year>2012</year></pub-date><volume>43</volume><issue>11</issue><fpage>1082</fpage><lpage>1090</lpage><pmc-comment>elocation-id from pubmed: 10.1038/ng.941</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="P3">Pulmonary function measures reflect respiratory health and predict mortality, and are used in the diagnosis of chronic obstructive pulmonary disease (COPD). We tested genome-wide association with the forced expiratory volume in 1 second (FEV<sub>1</sub>) and the ratio of FEV<sub>1</sub> to forced vital capacity (FVC) in 48,201 individuals of European ancestry, with follow-up of top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined <italic>P</italic><5×10<sup>−8</sup>) with pulmonary function, in or near <italic>MFAP2, TGFB2, HDAC4, RARB, MECOM</italic> (<italic>EVI1</italic>), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1, and <italic>KCNE2</italic>. Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function.</p></abstract></article-meta></front><body><sec sec-type="intro" id="S1"><title>Introduction</title><p id="P4">Pulmonary function, reliably measurable by spirometry, is a heritable trait reflecting the physiological state of the airways and lungs<sup><xref rid="R1" ref-type="bibr">1</xref></sup>. Pulmonary function measures are important predictors of population morbidity and mortality<sup><xref rid="R2" ref-type="bibr">2</xref>-<xref rid="R4" ref-type="bibr">4</xref></sup>, and are used in the diagnosis of chronic obstructive pulmonary disease (COPD), which ranks among the leading causes of death in developed and developing countries<sup><xref rid="R5" ref-type="bibr">5</xref>,<xref rid="R6" ref-type="bibr">6</xref></sup>. A reduced ratio of forced expiratory volume in 1 second (FEV<sub>1</sub>) to forced vital capacity (FVC) is used to define airway obstruction, and a reduced FEV<sub>1</sub> is used to grade the severity of airway obstruction<sup><xref rid="R7" ref-type="bibr">7</xref></sup>.</p><p id="P5">Recently, two large genome-wide association studies (GWAS), each comprising discovery sets of more than 20,000 individuals of European ancestry identified novel loci for lung function<sup><xref rid="R8" ref-type="bibr">8</xref>,<xref rid="R9" ref-type="bibr">9</xref></sup>. Recognizing the need for larger datasets to increase the power to detect loci of individually modest effect size, we conducted a meta-analysis of 23 lung function GWAS comprising a total of 48,201 individuals of European ancestry (Stage 1) and followed-up potentially novel loci in 17 further studies comprising up to 46,411 individuals (Stage 2). We identified 16 additional novel loci for lung function, and provided evidence corroborating association of loci previously associated with lung function<sup><xref rid="R8" ref-type="bibr">8</xref>-<xref rid="R11" ref-type="bibr">11</xref></sup>. Our findings implicate a number of different mechanisms underlying regulation of lung function and highlight loci shared with complex traits and diseases, including height, lung cancer, and myocardial infarction.</p></sec><sec sec-type="results" id="S2"><title>Results</title><sec id="S3"><title>Genome-wide analysis (stage 1)</title><p id="P6">Meta-analyses for cross-sectional lung function measures were undertaken for approximately 2.5 million genotyped or imputed SNPs across 23 studies with a combined sample size of 48,201 adult individuals of European ancestry. Characteristics of the cohort participants and the genotyping are shown in <xref ref-type="supplementary-material" rid="SD1">Supplementary Tables 1A and 1B</xref>. FEV<sub>1</sub> and FEV<sub>1</sub>/FVC were adjusted for ancestry principal components, age, age<sup>2</sup>, sex, and height as covariates. Association testing of the inverse-normal transformed residuals for FEV<sub>1</sub> and FEV<sub>1</sub>/FVC assumed an additive genetic model and was stratified by ever-smoking (versus never-smoking) status. Meta-analyses of the smoking strata within study, and the study-specific results, were undertaken using inverse variance weighting (the inverse of the standard error squared was used as the weight). We applied genomic control twice at study level (to each smoking stratum separately and to the study level pooled estimates) and also at meta-analysis level to avoid inflation of test statistics due to cryptic population structure or relatedness (see <xref ref-type="supplementary-material" rid="SD1">Supplementary Table 1A</xref> for study level estimates). Our application of genomic control at the three stages is likely to be overly conservative because it has recently been shown that in large meta-analyses, test statistics are expected to be elevated under polygenic inheritance even when there is no population structure<sup><xref rid="R12" ref-type="bibr">12</xref></sup>. Test statistic inflation (λ<sub>GC</sub>) prior to applying genomic control at meta-analysis level was 1.12 for FEV<sub>1</sub> and 1.09 for FEV<sub>1</sub>/FVC. Genomic inflation estimates increase with sample size, as has been shown for other traits<sup><xref rid="R13" ref-type="bibr">13</xref>-<xref rid="R15" ref-type="bibr">15</xref></sup>; standardised estimates to a sample of 1000 individuals (λ<sub>GC_1000</sub>) were 1.002 for FEV<sub>1</sub> and 1.002 for FEV<sub>1</sub>/FVC. Plots of meta-analysis <italic>P</italic>-values for FEV<sub>1</sub> and FEV<sub>1</sub>/FVC against a uniform distribution of <italic>P</italic> values expected under the null hypothesis showed deviations which were attenuated, but persisted, after removal of SNPs in loci reported previously, consistent with additional loci being associated with lung function (<xref ref-type="supplementary-material" rid="SD1">Supplementary Figure 1A</xref>).</p></sec><sec id="S4"><title>Follow-up analysis (stage 2)</title><p id="P7">Twenty-nine new loci showing evidence of association with lung function (<italic>P</italic><3×10<sup>−6</sup>) in Stage 1 were followed up in Stage 2 by utilizing <italic>in silico</italic> data from seven studies, and by undertaking additional genotyping in 10 studies for the 10 highest-ranked SNPs (<xref ref-type="fig" rid="F1">Figure 1</xref>). Full details of the SNP selection are given in the <xref ref-type="app" rid="APP1">Online Methods</xref>. Inverse variance weighting meta-analysis was performed across Stages 1 and 2, and two-sided p-values were obtained for the pooled estimates. Sixteen new loci reached genome-wide significance (<italic>P</italic><5×10<sup>−8</sup>) and showed consistent direction of effects in both stages, comprising 12 new loci for FEV<sub>1</sub>/FVC, 3 new loci for FEV<sub>1</sub>, and one new locus reaching genome-wide significance for both traits (<xref ref-type="fig" rid="F2">Figure 2</xref>, <xref ref-type="table" rid="T1">Table 1</xref>). To assess the heterogeneity across studies included in Stage 1 and Stage 2, Chi-square tests were undertaken for all 16 SNPs; and none of them was statistically significant after applying a Bonferroni correction for 16 tests. The sentinel SNPs at these loci were in or near the genes <italic>MFAP2</italic> (1p36.13), <italic>TGFB2/LYPLAL1</italic> (1q41), <italic>HDAC4/FLJ43879</italic> (2q37.3), <italic>RARB</italic> (3p24.2), <italic>MECOM</italic> (<italic>EVI1</italic>) (3q26.2), <italic>SPATA9/RHOBTB3</italic> (5q15), <italic>ARMC2</italic> (6q21), <italic>NCR3/AIF1</italic> (6p21.33), <italic>ZKSCAN3</italic> (6p22.1), <italic>CDC123</italic> (10p13), <italic>C10orf11</italic> (10q22.3), <italic>LRP1</italic> (12q13.3), <italic>CCDC38</italic> (12q22), <italic>MMP15</italic> (16q13), <italic>CFDP1</italic> (16q23.1) and <italic>KCNE2/C21orf82</italic> (21q22.11) (<xref ref-type="supplementary-material" rid="SD1">Supplementary Figures 1B and 1C</xref>). The strongest signals in <italic>AGER</italic> (rs2070600)<sup><xref rid="R8" ref-type="bibr">8</xref>,<xref rid="R9" ref-type="bibr">9</xref></sup> and two of the novel signals (rs6903823 in <italic>ZKSCAN3</italic> and rs2857595, upstream of <italic>NCR3</italic>) lie within a~3.8Mb interval at 6p21.32-22.1 which is characterised by long-range linkage disequilibrium. Nevertheless, the leading SNPs in these regions which are within the major histocompatibility complex (MHC) were statistically independent (<xref ref-type="supplementary-material" rid="SD1">Supplementary Note</xref>).</p></sec><sec id="S5"><title>Gene expression</title><p id="P8">We investigated mRNA expression of the nearest gene for each of the 16 novel loci in human lung tissue and in a range of human primary cells including lung, brain, airway smooth muscle cells and bronchial epithelial cells. Transcripts were detected for all selected genes in lung tissue except <italic>CCDC38</italic> and transcripts for most genes were also detected in airway smooth muscle cells and in bronchial epithelial cells (<xref ref-type="table" rid="T2">Table 2</xref>). As we were unable to detect expression of <italic>CCDC38</italic> in any tissue, we also examined expression of <italic>SNPRF</italic>, which is the adjacent gene (<xref ref-type="table" rid="T2">Table 2</xref>), and found expression in all four cell types. <italic>TGFB2, MFAP2, EVI1</italic> and <italic>MMP15</italic> were expressed in one or more lung cell types but not in peripheral blood mononuclear cells providing evidence that these genes may exhibit tissue-specific expression.</p><p id="P9">We assessed whether SNPs in these new regions, or their proxies (r<sup>2</sup>>0.6), were associated with gene expression using a database of expression-associated SNPs in lymphoblastoid cell lines<sup><xref rid="R16" ref-type="bibr">16</xref></sup>. Four loci showed regional (<italic>cis</italic>) effects on expression (<italic>P</italic><1×10<sup>−7</sup>, <xref ref-type="supplementary-material" rid="SD1">Supplementary Note</xref>). A proxy for our sentinel SNP in <italic>CFDP1</italic>, rs2865531, coincided with the peak of the expression signal for <italic>CFDP1</italic> and the strongest proxy for rs6903823 in <italic>ZKSCAN3</italic> coincided with the peak of expression for ZSCAN12.</p></sec><sec id="S6"><title>Plausible pathways for lung function involving new loci</title><p id="P10">The putative function of the genes within, or closest to, the association peaks identify a range of plausible mechanisms for impacting lung function. The most statistically significant new signal for FEV<sub>1</sub>/FVC (<italic>P</italic>=7.5×10<sup>−16</sup>) was in the gene encoding <italic>MFAP2</italic>, an antigen of elastin-associated microfibrils<sup><xref rid="R17" ref-type="bibr">17</xref></sup>, although correlated SNPs in the region potentially implicate other genes that could plausibly influence lung function, such as <italic>CROCC</italic>, which encodes rootletin, a component of cilia<sup><xref rid="R18" ref-type="bibr">18</xref></sup>. Our second strongest new signal, also for FEV<sub>1</sub>/FVC, was in the gene encoding the retinoic acid receptor beta (<italic>RARB</italic>). <italic>Rarb</italic>-null knockout mice exhibit premature alveolar septation<sup><xref rid="R19" ref-type="bibr">19</xref></sup>. The third most statistically significant new signal for FEV<sub>1</sub>/FVC, and the most statistically significant new signal for FEV<sub>1</sub>, was in <italic>CDC123</italic>. This was the only novel region to show genome-wide association with both traits. <italic>CDC123</italic> encodes a homologue of a yeast cell division cycle protein which plays a critical role in modulating Eukaryotic initiation factor 2 in times of cell stress<sup><xref rid="R20" ref-type="bibr">20</xref></sup>. The fourth signal for FEV<sub>1</sub>/FVC is downstream of <italic>HDAC4</italic> which encodes a histone deacetylase; reductions in the expression of other histone deacetylases (specifically HDAC2, HDAC5 and HDAC8) have been noted in COPD<sup><xref rid="R21" ref-type="bibr">21</xref></sup>. The regions we observed in the MHC are much more difficult to localize with multiple genes being tagged by the top SNP, including non-synonymous SNPs in ZKSCAN3, PGBD1, ZSCAN12, ZNF323, TCF19, LTA, C6orf15 and <italic>GPANK1</italic> (also known as <italic>BAT4</italic>) (<xref ref-type="supplementary-material" rid="SD1">Supplementary Table 2</xref>). At 6p21.33, the strongest association with lung function was observed for rs2857595, which is in linkage disequilibrium (LD, r<sup>2</sup>=0.47) with a non-synonymous SNP in <italic>LTA</italic> (encoding lymphotoxin alpha) and with a SNP in the upstream promoter region of <italic>TNFA</italic> (encoding tumour necrosis factor alpha, r<sup>2</sup>=0.86), both of which are plausible candidates<sup><xref rid="R22" ref-type="bibr">22</xref>,<xref rid="R23" ref-type="bibr">23</xref></sup>. Our top SNP in <italic>MMP15</italic> is in strong LD (r<sup>2</sup>=1) with a non-synonymous SNP (rs3743563, which has an association with FEV<sub>1</sub>/FVC at <italic>P</italic>=1.8×10<sup>−7</sup>) within the same gene. Plausible mechanisms implicated by the other novel signals of association with lung function reported here include TGF-beta signalling; <italic>TGFB2</italic> expression is upregulated in bronchial epithelial cells in asthma<sup><xref rid="R24" ref-type="bibr">24</xref></sup>. The putative function of key genes (as defined by LD with the leading SNP) in each of the 16 loci, and relevant findings from animal models, are summarised in <xref ref-type="table" rid="T2">Table 2</xref> and detailed in <xref ref-type="supplementary-material" rid="SD1">Supplementary Table 2</xref>.</p></sec><sec id="S7"><title>Associations with lung function in children</title><p id="P11">Alleles representing 11 of the 16 novel loci showed directionally consistent effects on lung function in 6,281 children (7 to 9 years of age) (<xref ref-type="supplementary-material" rid="SD1">Supplementary Table 3A</xref>) suggesting that genetic determination of lung function in adults may in part act via effects on lung development, or alternatively, that some genetic determinants of lung growth and lung function decline are shared.</p></sec><sec id="S8"><title>Association of lung function loci with other traits</title><p id="P12">Although we stratified for ever-smoking versus never-smoking, we did not adjust for the amount smoked. In order to investigate the possibility that the associations at any of our 16 novel regions were driven by an effect of the SNP on smoking behaviour, we evaluated <italic>in silico</italic> data for associations with smoking amount from the Ox-GSK consortium<sup><xref rid="R25" ref-type="bibr">25</xref></sup> for the leading SNPs in these 16 regions. None of these 16 SNPs showed statistically significant association with the number of cigarettes smoked per day (<xref ref-type="supplementary-material" rid="SD1">Supplementary Table 3B</xref>).</p><p id="P13">In addition, in our Stage 1 and Stage 2 datasets combined, we assessed whether the estimated effect sizes of the variants on lung function phenotypes differed substantially between ever-smokers and never-smokers (<xref ref-type="supplementary-material" rid="SD1">Supplementary Table 4</xref>) across the 16 loci. For the most strongly associated trait at each locus, we tested the SNP interaction with ever-smoking (versus never-smoking). None of the 16 novel loci showed a significant interaction (Bonferroni corrected threshold for 16 independent SNPs <italic>P</italic>=0.003125). These analyses suggest that the genetic effects we have identified underlie lung function variability irrespective of smoking exposure.</p><p id="P14">Our lung function associations were adjusted for height, but there are some overlaps between loci associated with height and those associated with lung function. Therefore, we evaluated <italic>in silico</italic> data for height associations of our novel regions in the GIANT consortium<sup><xref rid="R14" ref-type="bibr">14</xref></sup> dataset. The G allele of rs2284746 (<italic>MFAP2</italic>, intron), which was associated with decreased FEV<sub>1</sub>/FVC was associated with increased height (<xref ref-type="supplementary-material" rid="SD1">Supplementary Table 3C</xref>).</p><p id="P15">Given reported associations between lung cancer and either COPD or lung function decline, we also assessed <italic>in silico</italic> data for sentinel or proxy SNPs in these 16 regions for associations with lung cancer in the International Lung Cancer Consortium (ILCCO) GWAS meta-analysis<sup><xref rid="R26" ref-type="bibr">26</xref></sup>. Alleles associated with reduced lung function were associated with risk of lung cancer at the strongest available proxy SNP for rs2857595 (upstream of <italic>NCR3</italic>) at 6p21.33 (rs3099844, r<sup>2</sup>=0.67), and the strongest proxy SNP for rs6903823 (SNP in intron of <italic>ZKSCAN3</italic> and <italic>ZNF323</italic>) at 6p22.1 (rs209181, r<sup>2</sup>=0.69) (lung cancer associations, <italic>P</italic>=2.2×10<sup>−7</sup> and <italic>P</italic>=3.4×10<sup>−5</sup>, respectively, <xref ref-type="supplementary-material" rid="SD1">Supplementary Table 3D</xref>). No significant associations with lung cancer were seen at the other new loci (proxy SNPs were available for 15 of the 16 loci, Bonferroni corrected <italic>P</italic><0.0033).</p><p id="P16">In addition to the effects on height, smoking and lung cancer described above, we examined the literature for evidence for associations with other traits for each of the 16 new loci (detailed in <xref ref-type="supplementary-material" rid="SD1">Supplementary Table 2</xref>). Genome-wide significant associations (<italic>P</italic><5×10<sup>−8</sup>) have been reported in <italic>KCNE2</italic> with myocardial infarction<sup><xref rid="R27" ref-type="bibr">27</xref></sup>, and at 6p21.33 near <italic>NCR3</italic>/<italic>AIF1</italic>, with neonatal lupus<sup><xref rid="R28" ref-type="bibr">28</xref></sup> and with systemic lupus erythematosus<sup><xref rid="R29" ref-type="bibr">29</xref></sup>. Other significant complex disease associations have also been noted in the regions of <italic>CDC123</italic> (type 2 diabetes<sup><xref rid="R30" ref-type="bibr">30</xref></sup>), <italic>CFDP1</italic> (type 1 diabetes<sup><xref rid="R31" ref-type="bibr">31</xref></sup>) and <italic>MECOM</italic> (blood pressure<sup><xref rid="R32" ref-type="bibr">32</xref>,<xref rid="R33" ref-type="bibr">33</xref></sup>), but with weaker LD (r<sup>2</sup><0.3) between the reported SNP and the sentinel SNP for lung function in the region (<xref ref-type="supplementary-material" rid="SD1">Supplementary Table 2</xref>).</p></sec><sec id="S9"><title>Proportion of variance explained by loci discovered to date</title><p id="P17">Associations in 10 loci previously reported for lung function<sup><xref rid="R8" ref-type="bibr">8</xref>,<xref rid="R9" ref-type="bibr">9</xref></sup> reached genome-wide significance (<italic>P</italic><5×10<sup>−8</sup>) in our Stage 1 data, namely loci in or near <italic>TNS1, FAM13A, GSTCD</italic>/<italic>NPNT, HHIP, HTR4, ADAM19, AGER, GPR126, PTCH1</italic>, and <italic>TSHD4</italic> (<xref ref-type="supplementary-material" rid="SD1">Supplementary Table 5A</xref>). Thus, a total of 26 regions showed genome-wide significant association with lung function in our study. In aggregate, variants at these 26 regions explain approximately 3.2% of the additive polygenic variance for FEV<sub>1</sub>/FVC and 1.5% for FEV<sub>1</sub> (see <xref ref-type="supplementary-material" rid="SD1">Supplementary Note</xref>). Following the approach described by Park <italic>et al</italic>.<sup><xref rid="R34" ref-type="bibr">34</xref></sup> we estimated that there is a total of 102 (95% CI 57-155) independent variants with similar effect sizes to the 26 variants we report. In combination these 102 variants, comprising 26 discovered variants and 76 putative undiscovered variants, collectively explain around 7.5% of the additive polygenic variance for FEV<sub>1</sub>/FVC and 3.4% for FEV<sub>1</sub> (see <xref ref-type="supplementary-material" rid="SD1">Supplementary Table 6</xref>, <xref ref-type="app" rid="APP1">Online Methods</xref> and <xref ref-type="supplementary-material" rid="SD1">Supplementary Note</xref>).</p></sec></sec><sec sec-type="discussion" id="S10"><title>Discussion</title><p id="P18">In meta-analysis of 23 studies comprising 48,201 individuals of European ancestry and follow-up in 17 studies comprising up to 46,411 individuals, we report genome-wide significant associations with an additional 12 regions for FEV<sub>1</sub>/FVC, an additional three regions for FEV<sub>1</sub> and one additional region associated with both FEV<sub>1</sub> and FEV<sub>1</sub>/FVC. We also confirm genome-wide association with 10 regions previously associated with lung function, bringing to 26 the total number of loci associated with lung function in these data. Most of the new loci are in regions not previously suspected to have been involved in lung development, the control of pulmonary function or risk of developing COPD. Elucidating the mechanisms through which these regions influence lung function should lead to a more complete understanding of lung function regulation and the pathogenesis of COPD. Four of the new loci (<italic>MFAP2, ZKSCAN3</italic>, near <italic>NCR3</italic> and near <italic>KCNE2</italic>) we show to be associated with lung function are also associated with other complex traits and diseases (<italic>P</italic><5×10<sup>−8</sup> for the other trait at a SNP with r<sup>2</sup>>0.3 with the top lung function SNP in the region). Understanding the intermediates underlying these pleiotropic effects could also reveal crucial insights into the pathophysiology of lung disease. One potential explanation is that these loci underlie control of the mechanisms regulating the development and resolution of inflammation and subsequent tissue remodelling in a range of tissues.</p><p id="P19">The effect sizes of the variants in the 26 loci associated with lung function explain a modest proportion of the additive genetic variance in FEV<sub>1</sub>/FVC and in FEV<sub>1</sub>, even after accounting for putative undetected variants with a similar distribution of effect sizes<sup><xref rid="R34" ref-type="bibr">34</xref></sup>. Our findings are consistent with those from other common complex traits, where it is thought that many as yet unidentified common and rare sequence variants, and potentially structural variants could explain the remaining heritability<sup><xref rid="R35" ref-type="bibr">35</xref></sup>. That our study more than doubled the number of loci known to be associated with lung function underlines the utility of large sample sizes to achieve the power to detect common variants associated with complex traits. Nevertheless, it is likely that additional variants with similar effect sizes remain undiscovered<sup><xref rid="R14" ref-type="bibr">14</xref></sup>. In addition, our study was not designed to detect rare variants or structural variants associated with lung function. Identification of rare variants associated with lung function could be helpful in narrowing the scope of ongoing functional work to those genes most likely to be causally related to the association signals we detected.</p><p id="P20">Our study focused on cross-sectional measures of lung function. Adult lung function at a particular time point is influenced by the peak lung function achieved by 25-35 years of age, as well as the rate of decline of lung function after that peak<sup><xref rid="R36" ref-type="bibr">36</xref></sup>. The 26 loci now confirmed to be associated with lung function could affect either pre- or post-natal lung development and growth or decline in lung function during adulthood, or both. We showed consistent directions of estimated effects on lung function between adults and children at 7-9 years of age for SNPs at 11 of the 16 new loci, and eight of 10 previously reported loci (<xref ref-type="supplementary-material" rid="SD1">Supplementary Table 3A</xref>). The results we show for lung function in children provide some indication that these loci affect lung function development, although studies in larger populations of children would provide greater clarity for SNPs in the new loci. Further investigations will be required in large populations with longitudinal data to delineate the influence of these variants on the rates of development of, and decline in, lung function and on the risk of developing COPD.</p><p id="P21">Of the sentinel SNPs at the 16 new loci associated with lung function, only rs2284746 (<italic>MFAP2)</italic> was associated with height in the GIANT consortium<sup><xref rid="R14" ref-type="bibr">14</xref></sup> dataset. The G allele of rs2284746 was associated with both increased height and reduced lung function. A similar relationship between lung function and height was previously reported for the G allele of rs3817928 in <italic>GPR126</italic><sup><xref rid="R8" ref-type="bibr">8</xref>,<xref rid="R14" ref-type="bibr">14</xref></sup>, which is associated with decreased height, but with increased FEV<sub>1</sub>/FVC. A further three of the 180 loci found to be associated with height<sup><xref rid="R14" ref-type="bibr">14</xref></sup> showed association (for 180 loci, Bonferroni corrected threshold <italic>P</italic>=2.8×10<sup>−4</sup>) with either FEV<sub>1</sub> (<italic>CLIC4</italic> and <italic>BMP6</italic>) or FEV<sub>1</sub>/FVC (<italic>PIP4K2B</italic>) (<xref ref-type="supplementary-material" rid="SD1">Supplementary Table 3E</xref>). In each case, the allele associated with an increase in height was associated with a decrease in lung function. This is not the case for the association of rs1032296 near <italic>HHIP</italic>, which has shown consistent directions of effects on lung function and height<sup><xref rid="R14" ref-type="bibr">14</xref>,<xref rid="R11" ref-type="bibr">11</xref></sup>. However, the strongest SNP associated with height in the <italic>HHIP</italic> region lies within an intron of <italic>HHIP</italic> but shows no association with FEV<sub>1</sub> or FEV<sub>1</sub>/FVC. Furthermore, while height is an important predictor of FEV<sub>1</sub>, this is not true for its ratio to FVC<sup><xref rid="R37" ref-type="bibr">37</xref></sup>. These observations argue against the associations with lung function at these loci being simply due to incomplete adjustment for height.</p><p id="P22">We stratified by ever- and never-smoker status in our analyses and in our investigation of amount smoked in the Ox-GSK consortium<sup><xref rid="R25" ref-type="bibr">25</xref></sup> none of the sentinel SNPs in the 16 new regions showed association with the number of cigarettes smoked per day. Additionally, none of these regions was associated with ever-smoking in the Ox-GSK consortium data (<xref ref-type="supplementary-material" rid="SD1">Supplementary Table 3B</xref>). Thus the SNP associations with lung function we observed are unlikely to have arisen simply as a consequence of inadequate adjustment for smoking.</p><p id="P23">We did not observe any interactions with ever-smoking for any of the sentinel SNPs in the 16 new regions that exceeded a Bonferroni-corrected significance level (for 16 SNPs). Thus, the effects on lung function of the novel variants we identified are apparent in both ever-smokers and in never-smokers, and the effects of smoking and of these genetic variants may be independent and additive.</p><p id="P24">In other common complex diseases, follow up studies that incorporate common genetic risk variants into models to predict disease have not been shown to add substantially to existing risk models, particularly when such models already include family history<sup><xref rid="R38" ref-type="bibr">38</xref>,<xref rid="R39" ref-type="bibr">39</xref></sup>. The same may also prove to be true for the 26 genetic variants described in this paper, as the effect size of any individual variant is small, but further work is required in this area. The major utility of our findings will be in the knowledge they provide about previously unknown pathways underlying lung function. Elucidating the mechanisms that these genes are involved in will lead to improved understanding of the regulation of lung function and potentially to new therapeutic targets for COPD.</p></sec><sec sec-type="supplementary-material" id="SM"><title>Supplementary Material</title><supplementary-material content-type="local-data" id="SD1"><label>4</label><media xlink:href="NIHMS335195-supplement-4.pdf" mimetype="application" mime-subtype="pdf" orientation="portrait" xlink:type="simple" id="d37e3007" position="anchor"></media></supplementary-material></sec></body><back><ack id="S11"><title>Acknowledgements</title><p>We thank the many colleagues who contributed to collection and phenotypic characterization of the clinical sampling, genotyping, and analysis of the data. We especially thank those who kindly agreed to participate in the studies.</p><p>Major funding for this work is from the following sources (alphabetical): Academy of Finland (project grants 104781, 120315, 129269, 1114194, Center of Excellence in Complex Disease Genetics (213506 and 129680) and SALVE); Althingi (Icelandic Parliament); Arthritis Research Campaign; Asthma UK; AstraZeneca; AXA Research Fund; Biotechnology and Biological Sciences Research Council (BBSRC) (BB/F019394/1, G20234); British Heart Foundation (PG/97012, PG/06/154/22043, FS05/125); British Lung Foundation; Canadian Institutes of Health Research (Grant ID MOP-82893); Cancer Research United Kingdom; Chief Scientist Office, Scottish Government Health Directorate (CZD/16/6); Croatian Institute for Public Health; UK Department of Health; Dutch Kidney Foundation; Erasmus Medical Center and Erasmus University, Rotterdam; Estonian Genome Center, University of Tartu, Estonia (SF0180142s08); EU funding (GABRIEL GRANT Number: 018996, ECRHS II Coordination Number: QLK4-CT-1999-01237); European Commission (DG XII, EURO-BLCS, FP-5 QLG1-CT-2000-01643, FP-6 LSHB-CT-2006-018996 (GABRIEL), FP-6 LSHG-CT-2006-018947 (EUROSPAN), FP-6 GenomEUtwin project QLG2-CT-2002-01254, FP7/2007-2013: HEALTH-F2-2008-201865, GEFOS, HEALTH-F2-2008-35627, TREAT-OA, HEALTH-F4-2007-201413 (ENGAGE)); Finnish Foundation for Cardiovascular Research; Flight Attendant Medical Research Institute (FAMRI); German Asthma and COPD Network (COSYCONET: BMBF grant 01GI0883); German Bundesministerium fuer Forschung und Technology (01 AK 803 A-H, 01 IG 07015 G); German Federal Ministry of Education and Research (BMBF) (03ZIK012, 01ZZ9603, 01ZZ0103, and 01ZZ0403): German National Genome Research Network (NGFN-2 and NGFN-plus); German Ministry of Cultural Affairs; GlaxoSmithKline; Gyllenberg Foundations; Healthway, Western Australia; Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; Healthcare and Bioscience iNet (funded by the East Midlands Development Agency, part-financed by the European Regional Development Fund, delivered by Medilink East Midlands); Higher Education Funding Council for England (HEFCE); Hjartavernd (Icelandic Heart Association); Innsbruck Medical University; Institute for Anthropological Research in Zagreb; International Osteoporosis Foundation; Intramural Research Program of the NIH, National Institute on Aging and National Institute of Environmental Health Sciences; Jalmari and Rauha Ahokas Foundation; Juvenile Diabetes Research Foundation International (JDRF); Lifelong Health and Wellbeing Initiative (G0700704/84698); Medical Research Council UK (G1000861, G0501942, G0902313, G0000934, G0800582, G0500539, G0600705, PrevMetSyn/SALVE, G9901462); Medical Research Fund of the Tampere University Hospital; Ministry of Science, Education and Sport of the Republic of Croatia (108-1080315-0302); Medical Research Council Human Genetics Unit; Medisearch-The Leicester Medical Research Foundation; Munich Center of Health Sciences (MC Health) as part of LMUinnovativ; National Health and Medical Research Council of Australia (Grant ID 403981 and ID 003209); National Human Genome Research Institute (NHGRI) (U01-HG-004729, U01-HG-004402); National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centres (Guy’s & St Thomas’ NHS Foundation Trust in partnership with King’s College London and Cambridge University Hospitals NHS Foundation Trust in partnership with the University of Cambridge); Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) (050-060-810); Netherlands Organization for the Health Research and Development (ZonMw); Netherlands Organization of Scientific Research NOW (1750102007006, 175.010.2005.011, 911-03-012); Northern Netherlands Collaboration of Provinces (SNN); Norwegian University of Science and Technology; Novo Nordisk; Ontario Institute of Cancer Research and Canadian Cancer Society Research Institute (CCSRI 020214); Republic of Croatia Ministry of Science, Education and Sports research grants (108-1080315-0302); Research Institute for Diseases in the Elderly (RIDE) (014-93-015: RIDE2); Research Into Ageing (251); Siemens Healthcare, Erlangen, Germany and the Federal State of Mecklenburg- West Pomerania; Social Ministry of the Federal State of Mecklenburg-West Pomerania; Structure Enhancing Fund (FES) of the Dutch government; Swedish Heart and Lung Foundation grant 20050561; Swedish Research Council for Worklife and Social research (FAS), grants 2001-0263, 2003-0139; Swiss National Science Foundation (grants no 4026-28099,3347CO-108796, 3247BO-104283, 3247BO-104288, 3247BO-104284, 32-65896.01,32-59302.99, 32-52720.97, 32-4253.94); The Asthma, Allergy and Inflammation Research Trust; The Great Wine Estates of the Margaret River region of Western Australia; The Netherlands’ Ministry of Economic Affairs, Ministry of Education, Culture and Science and Ministry for Health, Welfare and Sports; The Royal Society; The University of Split and Zagreb Medical Schools,; Tromsø University; U01 DK062418; UBS Wealth Foundation Grant BA29s8Q7-DZZ; UK Department of Health Policy Research Programme; University Hospital Oulu, Biocenter, University of Oulu, Finland (75617); University Medical Center Groningen; University of Bristol; University of Leicester HEFCE CIF award; University of Nottingham; US National Institute of Health (NIH) (1P50 CA70907, RO1 CA121197, U19 CA148127, CA55769, CA127219, R01HL071051, R01HL071205, R01HL071250, R01HL071251, R01HL071252, R01HL071258, R01HL071259, UL1RR025005, contracts HHSN268200625226C, HHSN268200782096C, R01-HL084099); US NIH National Cancer Institute (RO1CA111703); US NIH National Center for Research Resources (grants M01-RR00425 and 5M01 RR00997); US NIH National Eye Institute (NEI); US NIH National Heart, Lung and Blood Institute (contracts N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, N01-HC-95095, N01-HC-48047, N01-HC-48048, N01-HC-48049, N01-HC-48050, N01-HC-45134, N01-HC-05187, N01-HC-45205, N01-HC-45204, N01 HC-25195, N01-HC-95159 through N01-HC-95169, RR-024156, N02-HL-6-4278, R01 HL-071022,R01 HL-077612, R01 HL-074104, RC1 HL100543, HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C, grants HL080295, HL087652, HL105756, R01-HL-084099, R01HL087641, R01HL59367,R01HL086694, HL088133, HL075336 5R01HL087679-02 through the STAMPEED program (1RL1MH083268-01), 1K23HL094531-01); US NIH National Institute of Allergy and Infectious Diseases (NIAID); US NIH National Institute of Child Health and Human Development (NICHD); US NIH National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (DK063491); US NIH National Institute of Environmental Health Sciences (NIEHS) (ZO1 ES49019, ES015794); US NIH National Institute of Mental Health (NIMH) (5R01MH63706:02); US NIH National Institute of Neurological Disorders and Stroke (NINDD); US NIH National Institute on Aging (NIA) (R01 AG032098, RC1 AG035835, N01AG12100, N01AG62101, N01AG62103, N01AG62106, 1R01AG032098-01A1, AG-023269, AG-15928, AG-20098, AG-027058); Wellcome Trust (077016/Z/05/Z, GR069224, 068545/Z/02, 076113/B/04/Z, 079895).</p></ack><fn-group><fn id="FN3"><p id="P40"><bold>AUTHOR CONTRIBUTIONS</bold></p><p id="P41">Author contributions are listed in alphabetical order. See <xref ref-type="supplementary-material" rid="SD1">Supplementary Note</xref> for definitions of study acronyms.</p><p id="P42"><bold>Project conception, design and management</bold>. <italic>Stage 1 GWAS, AGES:</italic> G.E., M.G., V.G., T.B.H., L.J.L. <italic>ARIC:</italic> S.J.L., N.F., L.R.L., D.J.C., D.B.H., B.R.J., A.C.M., K.E.N. <italic>B58C-T1DGC:</italic> D.P.S. <italic>B58C-WTCCC:</italic> D.P.S. <italic>BHS1:</italic> A.L.J., A.W.M., L.J.P., <italic>CHS:</italic> S.A.G., S.R.H., T.L., B.M.P. <italic>CROATIA-Korcula:</italic> H.C., I.G., S.J., I.R., A.F.W., L.Z. <italic>CROATIA-Vis:</italic> H.C., C.H., O.P., I.R., A.F.W. <italic>ECRHS:</italic> D.L.J., E.O., I.P, M.W. <italic>EPIC</italic>: N.J.W. <italic>FHS:</italic> J.B.W., G.T.O. <italic>FTC:</italic> J.K., K.H.P., T. Rantanen. <italic>Health ABC:</italic> M.C.A., P.A.C., T.B.H., S.B.K., Y.L., B.M. <italic>Health 2000:</italic> M.H., M.K. <italic>KORA F4:</italic> J. Heinrich. <italic>KORA S3:</italic> C.G., H.E.W. <italic>NFBC1966:</italic> P.E., A-L.H., M-R.J., A.P. <italic>ORCADES:</italic> H.C., S.H.W., J.F.W., A.F.W. <italic>RS:</italic> A. Hofman. <italic>SHIP:</italic> S.G., G.H., B.K., H.V. <italic>TwinsUK:</italic> T.D.S., G.Z. <italic>Stage 2 follow-up, ADONIX:</italic> J. Brisman., A-C.O. <italic>BHS2:</italic> J. Beilby. <italic>BRHS:</italic> R.W.M., S.G.W., P.H.W. <italic>BWHHS:</italic> G.D.S., S.E., D.A.L., P.H.W. <italic>CARDIA:</italic> A.S.<italic>CROATIA-Split:</italic> M.B., I.K., T.Z. <italic>GS:SFHS:</italic> C.M.J., S.M.K., A.D.M, D.J.P. <italic>HCS:</italic> C.C., J.W.H., A.A.S. <italic>LBC1936:</italic> I.J.D., S.E.H., J.M.S. <italic>LifeLines:</italic> H.M.B., D.S.P., J.M.V., C. W. <italic>MESA-Lung:</italic> R.G.B., J.L.H. <italic>Nottingham smokers:</italic> I.P.H. NSHD: R.H., D.K. <italic>SAPALDIA:</italic> N.P.-H., T. Rochat. <italic>Look-up studies, ALSPAC:</italic> R.G., J. Henderson. <italic>ILCCO:</italic> ILCCO data. <italic>Ox-GSK</italic>: C.F., J.M.</p><p id="P43"><bold>Phenotype collection and data management</bold>. <italic>Stage 1 GWAS, AGES:</italic> T.A. <italic>ARIC:</italic> D.J.C., N.F., L.R.L., A.C.M., K.E.N. <italic>B58C-T1DGC:</italic> A.R.R., D.P.S. <italic>B58C-WTCCC:</italic> A.R.R., D.P.S. <italic>BHS1:</italic> A.L.J., A.W.M., L.J.P. <italic>CHS:</italic> S.A.G., S.R.H., T.L., B.M.P.<italic>CROATIA-Korcula:</italic> I.G., S.J., O.P., I.R., L.Z. <italic>CROATIA-Vis:</italic> H.C., C.H., O.P., I.R., A.F.W. <italic>ECRHS:</italic> D.L.J., E.O., I.P, M.W. <italic>EPIC:</italic> N.J.W. <italic>FHS:</italic> J.B.W., G.T.O. <italic>FTC:</italic> J.K., K.H.P., T. Rantanen. <italic>Health ABC:</italic> P.A.C., B.M., W.T. <italic>Health 2000:</italic> M.H., M.K. <italic>KORA F4:</italic> S.K, H.S. <italic>KORA S3:</italic> N.P.-H. <italic>NFBC1966:</italic> P.E., A-L.H., M-R.J., A.P. <italic>ORCADES:</italic> H.C., S.H.W., J.F.W. <italic>RS:</italic> G.G.B, M.E., D.W.L., B.H.Ch.S. <italic>SHIP:</italic> S.G., B.K., H.V. <italic>TwinsUK:</italic> C.J.H., P.G.Hysi., M.M., T.D.S., G.Z. <italic>Stage 2 follow-up</italic>, ADONIX: J. Brisman., A-C.O. <italic>BHS2:</italic> J. Beilby., M.L.H. <italic>BRHS:</italic> R.W.M., S.G.W., P.H.W. <italic>BWHHS:</italic> G.D.S., S.E., D.A.L., P.H.W. <italic>CARDIA:</italic> O.D.W. <italic>CROATIA-Split:</italic> M.B., I.K., T.Z. <italic>GS:SFHS:</italic> C.M.J., A.D.M. <italic>HCS:</italic> C.C., K.A.J., A.A.S. <italic>LBC1936:</italic> I.J.D., L.M.L., J.M.S. <italic>LifeLines:</italic> D.S.P., J.M.V. <italic>MESA-Lung:</italic> R.G.B., J.L.H. <italic>Nottingham smokers:</italic> K.A.A-B., J.D.B., I.P.H., A. Henry., M.O., I. Sayers. <italic>NSHD:</italic> R.H., D.K. <italic>SAPALDIA:</italic> N.P-H. <italic>Look up studies, ALSPAC:</italic> R.G., J. Henderson. <italic>ILCCO:</italic> ILCCO. <italic>Raine:</italic> W.Q.A., P.G. Holt., C.E.P., P.D.S</p><p id="P44"><bold>Genotyping</bold>. <italic>Stage 1 GWAS, B58C-T1DGC:</italic> W.L.M. <italic>B58C-WTCCC:</italic> W.L.M. <italic>BHS1:</italic> A.L.J., A.W.M., L.J.P. <italic>CHS:</italic> S.R.H., B.M.P., J.I.R. <italic>CROATIA-Vis:</italic> C.H., I.R., A.F.W. <italic>ECRHS:</italic> M.W. <italic>EPIC:</italic> I.B., R.J.F.L., J.H.Z. <italic>FTC:</italic> J.K. <italic>Health ABC:</italic> Y.L., K.L. <italic>Health 2000:</italic> S.R., I. Surakka. <italic>KORA F4:</italic> N.K. <italic>KORA S3:</italic> C.G. <italic>NFBC1966:</italic> P.E., A-L.H., M-R.J., A.P., A.R. <italic>ORCADES:</italic> H.C., J.F.W. <italic>RS:</italic> F.R., A.G.U. <italic>SHIP:</italic> G.H. <italic>TwinsUK:</italic> C.J.H., S-Y.S. Stage 2 follow-up, <italic>ADONIX:</italic> S.D., F.N., A-C.O. <italic>BHS2:</italic> J. Beilby, G.C., J.H. <italic>BRHS:</italic> A.D.H., R.W.M. <italic>BWHHS:</italic> S.E., D.A.L. <italic>CARDIA:</italic> M.F., X.G. <italic>CROATIA-Split:</italic> V.B., T.Z. <italic>Gedling:</italic> J.R.B., T.M. <italic>GS:SFHS:</italic> C.M.J., S.M.K., D.J.P. <italic>HCS:</italic> J.W.H. <italic>LBC1936:</italic> I.J.D., S.E.H., L.M.L., J.M.S. <italic>LifeLines:</italic> C.W. <italic>MESA-Lung:</italic> S.S.R. <italic>NSHD:</italic> D.K., A.W. <italic>SAPALDIA:</italic> M.I., F.K. <italic>Look up studies, ALSPAC:</italic> S.M.R., W.L.M. <italic>ILCCO:</italic> ILCCO. <italic>Raine:</italic> W.Q.A., C.E.P.</p><p id="P45"><bold>Data analysis</bold>. <italic>Stage 1 GWAS, AGES:</italic> G.K.G., A.V.S. <italic>ARIC:</italic> N.F., D.B.H., L.R.L. <italic>B58C-T1DGC:</italic> A.R.R., D.P.S., <italic>B58C-WTCCC:</italic> A.R.R., D.P.S. <italic>BHS1:</italic> N.M.W. <italic>CHS:</italic> K.D.M., J.I.R. <italic>CROATIA-Korcula:</italic> C.H., J.E.H, V.V. <italic>CROATIA-Vis:</italic> C.H, V.V. <italic>ECRHS:</italic> D.L.J., A.R. <italic>EPIC:</italic> J.H.Z. <italic>FHS:</italic> J.B.W. <italic>FTC:</italic> I. Surakka. <italic>Health ABC:</italic> P.A.C., Y.L., K.L., W.T. <italic>Health 2000:</italic> M.K., S.R., I. Surakka. <italic>KORA S3:</italic> E.A. <italic>NFBC1966:</italic> A.R. <italic>ORCADES:</italic> C.H., V.V. <italic>RS:</italic> M.E., D.W.L. <italic>SHIP:</italic> S.G., G.H., B.K, H.V. <italic>TwinsUK:</italic> M.M., G.Z. <italic>Stage 2 follow-up studies, ADONIX:</italic> S.D., F.N. <italic>BHS2:</italic> G.C. <italic>BRHS:</italic> R.W.M. <italic>BWHHS:</italic> D.A.L. <italic>CARDIA:</italic> M.F., X.G. <italic>HCS:</italic> J.W.H., K.A.J. <italic>LBC1936:</italic> L.M.L. <italic>LifeLines:</italic> H.M.B. <italic>MESA-Lung:</italic> A.M., S.S.R. <italic>Nottingham smokers:</italic> I. Sayers., A. Henry. <italic>NSHD:</italic> D.G., R.H. <italic>SAPALDIA:</italic> I.C., M.I. <italic>Look up studies, ALSPAC:</italic> D.M.E. <italic>ILCCO:</italic> ILCCO. <italic>Ox-GSK:</italic> J.Z.L. <italic>Raine:</italic> W.Q.A.</p><p id="P46"><bold>Analysis group:</bold><italic>SpiroMeta consortium</italic>, I.P.H., T.J., M.S.A., M.D.T., L.V.W. <italic>CHARGE consortium</italic>, N.F., S.J.L., D.W.L., K.D.M., A.V.S., W.T., J.B.W.</p><p id="P47"><bold>Expression profiling and bioinformatics group:</bold><italic>SpiroMeta consortium</italic>, I.P.H., M.O., I.Sayers, M.S.A., M.D.T., L.V.W. <italic>CHARGE consortium</italic>, S.A.G., D.W.L.</p><p id="P48"><bold>Writing group:</bold><italic>SpiroMeta consortium</italic>, P.E., I.P.H., M.O., M.S.A., D.P.S., M.D.T., L.V.W. <italic>CHARGE consortium</italic>, S.J.L., D.W.L., S.A.G., G.T.O., V.G., B.H.Ch.S., W.T.</p></fn><fn id="FN4"><p id="P49"><bold>COMPETING FINANCIAL INTERESTS:</bold></p><p id="P50">Inês Barroso and spouse own stock in Incyte Ltd and GlaxoSmithKline. Fredrik Nyberg is employed by AstraZeneca R&D, 431 83 Mölndal, Sweden. Professor Postma has received unrestricted research grants from and has been consultant to AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Nycomed, TEVA. Clyde Francks is a full-time employee of the company GlaxoSmithKline (GSK) and GSK also funded several aspects of the study as detailed in the ACKNOWLEDGMENTS section for Ox-GSK.</p></fn></fn-group><app-group><app id="APP1"><title>APPENDIX</title><sec id="S12"><title>Online Methods</title><sec id="S13"><title>Study design</title><p id="P25">The study consisted of two stages. Stage 1 was a meta-analysis conducted on directly genotyped and imputed SNPs from individuals of European ancestry in 23 studies, with a total of 48,201 individuals. <xref ref-type="supplementary-material" rid="SD1">Supplementary Table 1A</xref> gives details of these studies. Thirty-four SNPs selected according to the results in Stage 1 were followed up in Stage 2. The ten leading SNPs were followed up in up to 46,411 individuals of European origin and the remaining 24 SNPs were followed up in a subset of up to 21,674 individuals (<xref ref-type="fig" rid="F1">Figure 1</xref>).</p></sec><sec id="S14"><title>Stage 1 samples</title><p id="P26">A total of 23 studies, 17 from the SpiroMeta consortium and six studies from the CHARGE consortium, formed Stage 1: AGES, ARIC, B58C T1DGC, B58C WTCCC, BHS1, CHS, ECRHS, EPIC (obese cases and population-based studies), the EUROSPAN studies (CROATIA-Korcula, ORCADES and CROATIA-Vis), FHS, FTC (incorporating the FinnTwin16 and Finnish Twin Study on Aging), Health 2000, Health ABC, KORA F4, KORA S3, NFBC1966, RS-I, RS-II, SHIP and TwinsUK-I (see <xref ref-type="supplementary-material" rid="SD1">Supplementary Table 1</xref> for definitions of abbreviations). Measurements of spirometry for each study are described in the <xref ref-type="supplementary-material" rid="SD1">Supplementary Note</xref>. The genotyping platforms and quality-control criteria implemented by each study are described in <xref ref-type="supplementary-material" rid="SD1">Supplementary Table 1B</xref>.</p></sec><sec id="S15"><title>Imputation</title><p id="P27">Imputation of non-genotyped SNPs was undertaken with MACH<sup><xref rid="R47" ref-type="bibr">47</xref></sup>, IMPUTE<sup><xref rid="R48" ref-type="bibr">48</xref></sup> or BIMBAM<sup><xref rid="R49" ref-type="bibr">49</xref></sup> with pre-imputation filters and parameters as shown in <xref ref-type="supplementary-material" rid="SD1">Supplementary Table 1B</xref>. SNPs were excluded if the imputation information, assessed using r2.hat (MACH), .info (IMPUTE) or OEvar (BIMBAM), was <0.3. In total, 2,706,349 SNPs were analyzed.</p></sec><sec id="S16"><title>Transformation of data and genotype-phenotype association analysis</title><p id="P28">Linear regression of age, age<sup>2</sup>, sex, height and ancestry principal components was undertaken on FEV<sub>1</sub> (milliliters) and FEV<sub>1</sub>/FVC (percent). The residuals were transformed to ranks and then transformed to normally distributed z-scores. These transformed residuals were then used as the phenotype for association testing under an additive genetic model, separately for ever-smokers and for never-smokers. The software used is specified in <xref ref-type="supplementary-material" rid="SD1">Supplementary Table 1B</xref>. Appropriate tests for association in related individuals were applied where necessary, as described in the <xref ref-type="supplementary-material" rid="SD1">Supplementary Note</xref>.</p></sec><sec id="S17"><title>Meta-analysis of Stage 1 data</title><p id="P29">All Stage 1 study effect estimates, both for ever-smokers and never-smokers were corrected using genomic control<sup><xref rid="R50" ref-type="bibr">50</xref></sup> and were oriented to the forward strand of the NCBI build 36 reference sequence of the human genome, consistently using the alphabetically higher allele as the coded allele. Study-specific lambda estimates are shown in <xref ref-type="supplementary-material" rid="SD1">Supplementary Table 1</xref>. For each study, effect estimates and standard errors for ever-smokers and never-smokers were meta-analysed using inverse variance weighting. Genomic control was applied again to the pooled effect-size estimates for each study. Finally effect-size estimates and standard errors were combined across studies using inverse variance weighting meta-analysis, and genomic control was applied to the pooled effect-size estimates. To describe the effect of imperfect imputation on power, for each SNP we report the effective sample size (<italic>N</italic> effective); the sum of the study-specific products of the sample size and the imputation quality metric. Meta-analysis statistics and figures were produced using R version 2.9.2.</p></sec><sec id="S18"><title>Selection of SNPs for Stage 2</title><p id="P30">All regions selected for follow-up in Stage 2 contained a lead SNP with novel evidence of association (all with <italic>P</italic><3×10<sup>−6</sup>) with FEV<sub>1</sub> and/or FEV<sub>1</sub>/FVC, an N effective ≥70% of the total Stage 1 sample size and the association signals from surrounding SNPs were consistent with their correlation (linkage disequilibrium) with the leading SNP. Twenty-nine independent regions with a leading SNP meeting these criteria were assessed in Stage 2. Regions were defined as independent if the leading SNP from one region was >500kb from the leading SNP of any other region. Long range linkage disequilibrium was also investigated between leading SNPs of regions in or near the MHC on chromosome 6 (<xref ref-type="supplementary-material" rid="SD1">Supplementary Note</xref>). For two regions, the leading SNP had an N effective ≥70% but <80% of the Stage 1 sample size and therefore a proxy SNP (r<sup>2</sup>=1 and 0.97) was also taken forward. For three regions, there were different leading SNPs for FEV<sub>1</sub> and FEV<sub>1</sub>/FVC and so both leading SNPs were assessed. A total of 34 SNPs were analysed in Stage 2 and are listed in <xref ref-type="supplementary-material" rid="SD1">Supplementary Table 5B</xref>. Previously reported regions<sup><xref rid="R8" ref-type="bibr">8</xref>-<xref rid="R11" ref-type="bibr">11</xref>,<xref rid="R51" ref-type="bibr">51</xref>,<xref rid="R52" ref-type="bibr">52</xref></sup> were not followed up. We present association test statistics in Stage 1 only for relevant SNPs from previously reported regions in <xref ref-type="supplementary-material" rid="SD1">Supplementary Table 5A</xref>.</p></sec><sec id="S19"><title>Stage 2 samples</title><p id="P31">The 34 SNPs were followed up in up to 11,275 individuals from seven studies with <italic>in silico</italic> data; CARDIA, CROATIA-Split, LifeLines, LBC1936, MESA-Lung, RS-III and TwinsUK-II (<xref ref-type="supplementary-material" rid="SD1">Supplementary Table 1</xref>). SNP rs2647044 was not available from TwinsUK-II.</p><p id="P32">The 34 SNPs were ranked by <italic>P</italic> value (for association with either FEV<sub>1</sub> or FEV<sub>1</sub>/FVC) and the top ten leading SNPs selected for follow up by genotyping in up to 35,136 individuals from ADONIX, BHS2, BRHS, BWHHS, Gedling, GS:SFHS, HCS, Nottingham Smokers, NSHD and SAPALDIA (<xref ref-type="supplementary-material" rid="SD1">Supplementary Table 1</xref>). If a SNP within the top ten had an N effective <80%, only the proxy SNP was included in the top ten for follow up. For regions which showed association with both FEV<sub>1</sub> and FEV<sub>1</sub>/FVC, only the leading SNP with the lowest <italic>P</italic> value for either trait was included if it was within the top ten SNPs. The study design is illustrated in <xref ref-type="fig" rid="F1">Figure 1</xref>.</p></sec><sec id="S20"><title>Meta-analysis of Stage 2 data</title><p id="P33">All Stage 2 studies provided effect estimates for ever-smokers and never-smokers, apart from Nottingham Smokers since they only had smokers. Studies with family data (BHS2 and GS:SFHS) analysed ever- and never-smokers together to account for the family correlation, adding the smoking status as a covariate in the model, and therefore provided smoking adjusted effect estimates. All Stage 2 study effect estimates were oriented to the forward strand of the NCBI build 36 reference sequence of the human genome, consistently using the alphabetically higher allele as the coded allele. For each study with separate results for ever- and for never-smokers, effect estimates and standard errors for ever- and never-smokers were meta-analysed using inverse variance weighting. Genomic control was applied to the pooled effect sizes of those studies with <italic>in silico</italic> data that undertook the analysis genome-wide. Effect estimates and standard errors were combined across Stage 2 studies using inverse variance weighting meta-analysis.</p></sec><sec id="S21"><title>Combined analysis of Stage 1 and Stage 2 samples</title><p id="P34">Meta-analysis of Stage 1 and Stage 2 results was undertaken using inverse variance weighting. We described associations as genome-wide significant if <italic>P</italic><5×10<sup>−8</sup>.</p></sec><sec id="S22"><title>PCR expression profiling</title><p id="P35">The mRNA expression profiles of <italic>TGFB2, MFAP2, HDAC4, EVI1, RARB</italic>, SPATA9, ARMC2, NCR3, CDC123, LRP1, CCDC38, SNRPF, MMP15, CFDP1, ZKSCAN3, KCNE2 and <italic>C10orf11</italic> were determined in human lung tissue and primary cell samples using RT-PCR, including RNA from lung (Ambion/ABI), brain, airway smooth muscle cells and human bronchial epithelial cells (Clonetics42). Primer sequences are listed in <xref ref-type="supplementary-material" rid="SD1">Supplementary Table 2</xref>. Full details are provided in the <xref ref-type="supplementary-material" rid="SD1">Supplementary Note</xref>.</p></sec><sec id="S23"><title>Lung function associations in our data of SNPs previously associated with lung function</title><p id="P36">In order to permit comparison of findings with recent studies of relevance to the field, we present association test statistics (in Stage 1 only) for relevant SNPs from previously reported regions (<xref ref-type="supplementary-material" rid="SD1">Supplementary Table 5A</xref>). We included regions: (i) reported as showing genome-wide significant association (<italic>P</italic><5×10<sup>−8</sup>) with lung function; (ii) reported as showing genome-wide significant association with COPD, providing that there was additional evidence of association with lung function and; (iii) <italic>DAAM2</italic>, which reached borderline significance in the SpiroMeta consortium<sup><xref rid="R9" ref-type="bibr">9</xref></sup>. Within each of these regions, if multiple SNPs had been reported, we included all relevant SNPs and also the SNP that showed the strongest association in our data.</p></sec><sec id="S24"><title>Association to other traits of lung function associated SNPs</title><p id="P37">Regions associated (<italic>P</italic><5×10<sup>−8</sup>) with lung function or COPD (and also associated with lung function) were looked up for other traits. Where multiple SNPs were reported for different traits or by different investigators, we aimed to include all relevant SNPs, except those with r<sup>2</sup>>0.9 with another SNP in the region. We also included the SNPs that showed the strongest association in our data for each region. The following related traits were assessed: (i) lung function in children (<xref ref-type="supplementary-material" rid="SD1">Supplementary Table 3A</xref>); (ii) smoking amount and ever-smoking versus never-smoking in the Ox-GSK consortium<sup><xref rid="R25" ref-type="bibr">25</xref></sup> dataset (<xref ref-type="supplementary-material" rid="SD1">Supplementary Table 3B</xref>); (iii) height in the GIANT consortium<sup><xref rid="R14" ref-type="bibr">14</xref></sup> dataset (<xref ref-type="supplementary-material" rid="SD1">Supplementary Table 3C and 3E</xref>) and (iv) lung cancer in the International Lung Cancer Consortium (ILCCO) GWAS meta-analysis<sup><xref rid="R26" ref-type="bibr">26</xref></sup> (<xref ref-type="supplementary-material" rid="SD1">Supplementary Table 3D</xref>).</p></sec><sec id="S25"><title>Estimation of the number of undiscovered variants and calculation of the proportion of variance explained</title><p id="P38">We used the approach proposed by Park <italic>et al</italic>.<sup><xref rid="R34" ref-type="bibr">34</xref></sup> to estimate the number of independent variants associated with lung function measures that have similar effect sizes to the variants already reported, and to calculate the proportion of the variance explained by them. We excluded discovery data when estimating effect sizes to avoid winner’s curse bias, and obtained the number of undiscovered variants using the discovery power to detect the unbiased effect sizes (<xref ref-type="supplementary-material" rid="SD1">Supplementary Table 6</xref> and <xref ref-type="supplementary-material" rid="SD1">Supplementary Note</xref>).</p></sec><sec id="S26"><title>Additional analyses</title><p id="P39">The top SNPs from our novel loci, and proxies, were searched for correlation with known common copy number variants and expression SNPs. Analyses to identify common pathways underlying the association signals for lung function were undertaken using MAGENTA v2<sup><xref rid="R53" ref-type="bibr">53</xref></sup> and GRAIL<sup><xref rid="R54" ref-type="bibr">54</xref></sup>. 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deletions</article-title><source>PLoS Genet</source><year>2009</year><volume>5</volume><fpage>e1000534</fpage><pub-id pub-id-type="pmid">19557189</pub-id></element-citation></ref></ref-list></back><floats-group><fig id="F1" orientation="portrait" position="float"><label>Figure 1</label><caption><p>Study design. A total of 34 SNPs showing novel evidence of association (<italic>P</italic><3×10<sup>−6</sup>) with FEV<sub>1</sub> and/or FEV<sub>1</sub>/FVC in a meta-analysis of the Stage 1 studies were followed up in Stage 2. Studies with a combined total of 24,737 individuals undertook genotyping and association testing of the top 10 SNPs. Seven studies (*) with a combined total of 11,275 individuals had genome-wide association data and provided results for up to 34 SNPs. <sup>#</sup>GS:SFHS undertook genotyping on a 32-SNP multiplex genotyping platform and so included the 32 top ranking SNPs (including proxies and both SNPs from regions which showed association with both FEV<sub>1</sub> and FEV<sub>1</sub>/FVC). This assay failed for one SNP (rs3769124) which was subsequently replaced with the 33<sup>rd</sup> SNP (rs4762767). SNP rs2284746 was excluded due to poor clustering. Although rs3743563 was chosen as proxy for rs12447804 which had N effective <80% in the Stage 1 meta-analysis, BHS2 were unable to genotype rs3743563 and so undertook genotyping for rs12447804 instead. See <xref ref-type="table" rid="T1">Table 1</xref> for definitions of abbreviations.</p></caption><graphic xlink:href="nihms-335195-f0001"></graphic></fig><fig id="F2" orientation="portrait" position="float"><label>Figure 2</label><caption><p>Manhattan plots of association results for (a) FEV<sub>1</sub>/FVC and (b) FEV<sub>1</sub>. Manhattan plots ordered by chromosome position. SNPs for which −log<sub>10</sub><italic>P</italic>>5 are indicated in red. Novel regions which reached genome-wide significance after Stage 1 + Stage 2 are labelled.</p></caption><graphic xlink:href="nihms-335195-f0002"></graphic><graphic xlink:href="nihms-335195-f0003"></graphic></fig><table-wrap id="T1" position="float" orientation="landscape"><label>Table 1</label><caption><p>Loci associated with lung function. Shown are FEV<sub>1</sub> and FEV<sub>1</sub>/FVC results for the leading SNPs, ordered by chromosome and position, for each independent locus associated (<italic>P</italic> <5×10<sup>−8</sup>) with FEV<sub>1</sub> or FEV<sub>1</sub>/FVC in a joint analysis of up to 94,612 individuals of European ancestry from the SpiroMeta-CHARGE GWAS (Stage 1) and follow-up (Stage 2). Two-sided p-values are given for Stage 1, Stage 2 and the joint meta-analysis of all stages. P-values reaching genome-wide significance (<italic>P</italic><5×10<sup>−8</sup>) in the joint meta-analysis of all stages are indicated in bold. SNPs reaching independent replication in Stage 2 (<italic>P</italic>=0.05/34 = 1.47×10<sup>−3</sup>) are indicated with their Stage 2 p-value in bold. The sample sizes (<italic>N</italic>) shown are the effective sample sizes. Effective sample size within each study is the product of sample size and imputation quality metric. Joint meta-analysis includes data from Stage 1 and Stage 2. Beta values reflect effect-size estimates on an inverse-normal transformed scale after adjustments for age, age<sup>2</sup>, sex, height and ancestry principal components. The estimated proportion of the variance explained by each SNP can be found in <xref ref-type="supplementary-material" rid="SD1">Supplementary Table 6</xref>.</p></caption><table frame="box" rules="all"><thead><tr><th rowspan="2" align="left" valign="bottom" colspan="1">Chr.</th><th rowspan="2" align="left" valign="bottom" colspan="1">SNP_ID(NCBI36 position), function</th><th rowspan="2" align="left" valign="bottom" colspan="1">Coded<break></break>allele<break></break>freq.</th><th rowspan="2" align="left" valign="bottom" colspan="1">Measure</th><th colspan="4" align="center" valign="bottom" rowspan="1">Stage 1</th><th colspan="4" align="center" valign="bottom" rowspan="1">Stage 2</th><th colspan="2" align="center" valign="bottom" rowspan="1">Joint meta-analysis of<break></break>all stages</th></tr><tr><th align="left" valign="bottom" rowspan="1" colspan="1">Beta (s.e.m.)</th><th align="left" valign="bottom" rowspan="1" colspan="1">P</th><th align="left" valign="bottom" rowspan="1" colspan="1">Coded<break></break>allele freq.</th><th align="left" valign="bottom" rowspan="1" colspan="1">N</th><th align="left" valign="bottom" rowspan="1" colspan="1">Beta (s.e.m.)</th><th align="left" valign="bottom" rowspan="1" colspan="1">P</th><th align="left" valign="bottom" rowspan="1" colspan="1">Coded<break></break>allele freq.</th><th align="left" valign="bottom" rowspan="1" colspan="1">N</th><th align="left" valign="bottom" rowspan="1" colspan="1">Beta (s.e.m.)</th><th align="left" valign="bottom" rowspan="1" colspan="1">P</th></tr></thead><tbody><tr><td rowspan="2" align="left" valign="middle" colspan="1">1</td><td rowspan="2" align="left" valign="middle" colspan="1">rs2284746(17179262), MFAP2(intron)</td><td rowspan="2" align="left" valign="middle" colspan="1">G</td><td align="left" valign="middle" rowspan="1" colspan="1">FEV<sub>1</sub>/FVC</td><td align="left" valign="middle" rowspan="1" colspan="1">−0.042 (0.007)</td><td align="left" valign="middle" rowspan="1" colspan="1">2.47E-09</td><td rowspan="2" align="left" valign="middle" colspan="1">0.516</td><td rowspan="2" align="left" valign="middle" colspan="1">45944</td><td align="left" valign="middle" rowspan="1" colspan="1">−0.038 (0.007)</td><td align="left" valign="middle" rowspan="1" colspan="1">2.64E-07</td><td rowspan="2" align="left" valign="middle" colspan="1">0.522</td><td rowspan="2" align="left" valign="middle" colspan="1">35371</td><td align="left" valign="middle" rowspan="1" colspan="1">−0.04 (0.005)</td><td align="left" valign="middle" rowspan="1" colspan="1">7.50E-16</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">FEV<sub>1</sub></td><td align="left" valign="middle" rowspan="1" colspan="1">0.008 (0.007)</td><td align="left" valign="middle" rowspan="1" colspan="1">2.78E-01</td><td align="left" valign="middle" rowspan="1" colspan="1">0.006 (0.007)</td><td align="left" valign="middle" rowspan="1" colspan="1">3.70E-01</td><td align="left" valign="middle" rowspan="1" colspan="1">0.007 (0.005)</td><td align="left" valign="middle" rowspan="1" colspan="1">1.48E-01</td></tr><tr><td rowspan="2" align="left" valign="middle" colspan="1">1</td><td rowspan="2" align="left" valign="middle" colspan="1">rs993925(216926691), TGFB2(downstream)</td><td rowspan="2" align="left" valign="middle" colspan="1">T</td><td align="left" valign="middle" rowspan="1" colspan="1">FEV<sub>1</sub>/FVC</td><td align="left" valign="middle" rowspan="1" colspan="1">0.04 (0.007)</td><td align="left" valign="middle" rowspan="1" colspan="1">2.54E-07</td><td rowspan="2" align="left" valign="middle" colspan="1">0.308</td><td rowspan="2" align="left" valign="middle" colspan="1">42402</td><td align="left" valign="middle" rowspan="1" colspan="1">0.023 (0.01)</td><td align="left" valign="middle" rowspan="1" colspan="1">1.76E-02</td><td rowspan="2" align="left" valign="middle" colspan="1">0.348</td><td rowspan="2" align="left" valign="middle" colspan="1">21414</td><td align="left" valign="middle" rowspan="1" colspan="1">0.034 (0.006)</td><td align="left" valign="middle" rowspan="1" colspan="1">1.16E-08</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">FEV<sub>1</sub></td><td align="left" valign="middle" rowspan="1" colspan="1">0.025 (0.007)</td><td align="left" valign="middle" rowspan="1" colspan="1">1.51E-03</td><td align="left" valign="middle" rowspan="1" colspan="1">0.003 (0.007)</td><td align="left" valign="middle" rowspan="1" colspan="1">7.29E-01</td><td align="left" valign="middle" rowspan="1" colspan="1">0.014 (0.005)</td><td align="left" valign="middle" rowspan="1" colspan="1">8.71E-03</td></tr><tr><td rowspan="2" align="left" valign="middle" colspan="1">2</td><td rowspan="2" align="left" valign="middle" colspan="1">rs12477314(239542085), HDAC4(downstream)</td><td rowspan="2" align="left" valign="middle" colspan="1">T</td><td align="left" valign="middle" rowspan="1" colspan="1">FEV<sub>1</sub>/FVC</td><td align="left" valign="middle" rowspan="1" colspan="1">0.052 (0.008)</td><td align="left" valign="middle" rowspan="1" colspan="1">4.48E-09</td><td rowspan="2" align="left" valign="middle" colspan="1">0.202</td><td rowspan="2" align="left" valign="middle" colspan="1">45585</td><td align="left" valign="middle" rowspan="1" colspan="1">0.031 (0.008)</td><td align="left" valign="middle" rowspan="1" colspan="1">8.41E-05</td><td rowspan="2" align="left" valign="middle" colspan="1">0.206</td><td rowspan="2" align="left" valign="middle" colspan="1">45821</td><td align="left" valign="middle" rowspan="1" colspan="1">0.041 (0.006)</td><td align="left" valign="middle" rowspan="1" colspan="1">1.68E-12</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">FEV<sub>1</sub></td><td align="left" valign="middle" rowspan="1" colspan="1">0.032 (0.008)</td><td align="left" valign="middle" rowspan="1" colspan="1">2.77E-04</td><td align="left" valign="middle" rowspan="1" colspan="1">0.025 (0.007)</td><td align="left" valign="middle" rowspan="1" colspan="1">1.82E-04</td><td align="left" valign="middle" rowspan="1" colspan="1">0.028 (0.005)</td><td align="left" valign="middle" rowspan="1" colspan="1">1.02E-07</td></tr><tr><td rowspan="2" align="left" valign="middle" colspan="1">3</td><td rowspan="2" align="left" valign="middle" colspan="1">rs1529672(25495586), RARB(intron)</td><td rowspan="2" align="left" valign="middle" colspan="1">C</td><td align="left" valign="middle" rowspan="1" colspan="1">FEV<sub>1</sub>/FVC</td><td align="left" valign="middle" rowspan="1" colspan="1">−0.06 (0.009)</td><td align="left" valign="middle" rowspan="1" colspan="1">7.75E-10</td><td rowspan="2" align="left" valign="middle" colspan="1">0.829</td><td rowspan="2" align="left" valign="middle" colspan="1">40624</td><td align="left" valign="middle" rowspan="1" colspan="1">−0.038 (0.009)</td><td align="left" valign="middle" rowspan="1" colspan="1">1.16E-05</td><td rowspan="2" align="left" valign="middle" colspan="1">0.831</td><td rowspan="2" align="left" valign="middle" colspan="1">45466</td><td align="left" valign="middle" rowspan="1" colspan="1">−0.048 (0.006)</td><td align="left" valign="middle" rowspan="1" colspan="1">3.97E-14</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">FEV<sub>1</sub></td><td align="left" valign="middle" rowspan="1" colspan="1">−0.037 (0.009)</td><td align="left" valign="middle" rowspan="1" colspan="1">1.78E-04</td><td align="left" valign="middle" rowspan="1" colspan="1">−0.011 (0.007)</td><td align="left" valign="middle" rowspan="1" colspan="1">9.33E-02</td><td align="left" valign="middle" rowspan="1" colspan="1">−0.02 (0.006)</td><td align="left" valign="middle" rowspan="1" colspan="1">2.16E-04</td></tr><tr><td rowspan="2" align="left" valign="middle" colspan="1">3</td><td rowspan="2" align="left" valign="middle" colspan="1">rs1344555(170782913), MECOM(intron)</td><td rowspan="2" align="left" valign="middle" colspan="1">T</td><td align="left" valign="middle" rowspan="1" colspan="1">FEV<sub>1</sub>/FVC</td><td align="left" valign="middle" rowspan="1" colspan="1">−0.019 (0.008)</td><td align="left" valign="middle" rowspan="1" colspan="1">2.61E-02</td><td rowspan="2" align="left" valign="middle" colspan="1">0.205</td><td rowspan="2" align="left" valign="middle" colspan="1">46067</td><td align="left" valign="middle" rowspan="1" colspan="1">−0.017 (0.012)</td><td align="left" valign="middle" rowspan="1" colspan="1">1.55E-01</td><td rowspan="2" align="left" valign="middle" colspan="1">0.209</td><td rowspan="2" align="left" valign="middle" colspan="1">21313</td><td align="left" valign="middle" rowspan="1" colspan="1">−0.018 (0.007)</td><td align="left" valign="middle" rowspan="1" colspan="1">6.65E-03</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">FEV<sub>1</sub></td><td align="left" valign="middle" rowspan="1" colspan="1">−0.042 (0.008)</td><td align="left" valign="middle" rowspan="1" colspan="1">1.91E-06</td><td align="left" valign="middle" rowspan="1" colspan="1">−0.025 (0.009)</td><td align="left" valign="middle" rowspan="1" colspan="1">6.44E-03</td><td align="left" valign="middle" rowspan="1" colspan="1">−0.034 (0.006)</td><td align="left" valign="middle" rowspan="1" colspan="1">2.65E-08</td></tr><tr><td rowspan="2" align="left" valign="middle" colspan="1">5</td><td rowspan="2" align="left" valign="middle" colspan="1">rs153916(95062456), SPATA9(upstream)</td><td rowspan="2" align="left" valign="middle" colspan="1">T</td><td align="left" valign="middle" rowspan="1" colspan="1">FEV<sub>1</sub>/FVC</td><td align="left" valign="middle" rowspan="1" colspan="1">−0.033 (0.007)</td><td align="left" valign="middle" rowspan="1" colspan="1">2.06E-06</td><td rowspan="2" align="left" valign="middle" colspan="1">0.552</td><td rowspan="2" align="left" valign="middle" colspan="1">47530</td><td align="left" valign="middle" rowspan="1" colspan="1">−0.025 (0.009)</td><td align="left" valign="middle" rowspan="1" colspan="1">6.67E-03</td><td rowspan="2" align="left" valign="middle" colspan="1">0.535</td><td rowspan="2" align="left" valign="middle" colspan="1">21647</td><td align="left" valign="middle" rowspan="1" colspan="1">−0.031 (0.005)</td><td align="left" valign="middle" rowspan="1" colspan="1">2.12E-08</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">FEV<sub>1</sub></td><td align="left" valign="middle" rowspan="1" colspan="1">−0.001 (0.007)</td><td align="left" valign="middle" rowspan="1" colspan="1">8.91E-01</td><td align="left" valign="middle" rowspan="1" colspan="1">0.004 (0.007)</td><td align="left" valign="middle" rowspan="1" colspan="1">6.22E-01</td><td align="left" valign="middle" rowspan="1" colspan="1">0.001 (0.005)</td><td align="left" valign="middle" rowspan="1" colspan="1">8.20E-01</td></tr><tr><td rowspan="2" align="left" valign="middle" colspan="1">6</td><td rowspan="2" align="left" valign="middle" colspan="1">rs6903823(28430275), ZKSCAN3(intron)/ZNF323(intron)</td><td rowspan="2" align="left" valign="middle" colspan="1">G</td><td align="left" valign="middle" rowspan="1" colspan="1">FEV<sub>1</sub>/FVC</td><td align="left" valign="middle" rowspan="1" colspan="1">−0.027 (0.008)</td><td align="left" valign="middle" rowspan="1" colspan="1">2.28E-03</td><td rowspan="2" align="left" valign="middle" colspan="1">0.209</td><td rowspan="2" align="left" valign="middle" colspan="1">47057</td><td align="left" valign="middle" rowspan="1" colspan="1">−0.013 (0.011)</td><td align="left" valign="middle" rowspan="1" colspan="1">2.34E-01</td><td rowspan="2" align="left" valign="middle" colspan="1">0.246</td><td rowspan="2" align="left" valign="middle" colspan="1">21489</td><td align="left" valign="middle" rowspan="1" colspan="1">−0.021 (0.007)</td><td align="left" valign="middle" rowspan="1" colspan="1">1.19E-03</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">FEV<sub>1</sub></td><td align="left" valign="middle" rowspan="1" colspan="1">−0.046 (0.008)</td><td align="left" valign="middle" rowspan="1" colspan="1">2.00E-07</td><td align="left" valign="middle" rowspan="1" colspan="1">−0.029 (0.008)</td><td align="left" valign="middle" rowspan="1" colspan="1">4.75E-04</td><td align="left" valign="middle" rowspan="1" colspan="1">−0.037 (0.006)</td><td align="left" valign="middle" rowspan="1" colspan="1">2.18E-10</td></tr><tr><td rowspan="2" align="left" valign="middle" colspan="1">6</td><td rowspan="2" align="left" valign="middle" colspan="1">rs2857595(31676448), NCR3(upstream)</td><td rowspan="2" align="left" valign="middle" colspan="1">G</td><td align="left" valign="middle" rowspan="1" colspan="1">FEV<sub>1</sub>/FVC</td><td align="left" valign="middle" rowspan="1" colspan="1">0.049 (0.009)</td><td align="left" valign="middle" rowspan="1" colspan="1">7.86E-08</td><td rowspan="2" align="left" valign="middle" colspan="1">0.809</td><td rowspan="2" align="left" valign="middle" colspan="1">45540</td><td align="left" valign="middle" rowspan="1" colspan="1">0.028 (0.008)</td><td align="left" valign="middle" rowspan="1" colspan="1">5.36E-04</td><td rowspan="2" align="left" valign="middle" colspan="1">0.796</td><td rowspan="2" align="left" valign="middle" colspan="1">46107</td><td align="left" valign="middle" rowspan="1" colspan="1">0.037 (0.006)</td><td align="left" valign="middle" rowspan="1" colspan="1">2.28E-10</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">FEV<sub>1</sub></td><td align="left" valign="middle" rowspan="1" colspan="1">0.04 (0.009)</td><td align="left" valign="middle" rowspan="1" colspan="1">1.46E-05</td><td align="left" valign="middle" rowspan="1" colspan="1">0.017 (0.007)</td><td align="left" valign="middle" rowspan="1" colspan="1">9.41E-03</td><td align="left" valign="middle" rowspan="1" colspan="1">0.025 (0.005)</td><td align="left" valign="middle" rowspan="1" colspan="1">1.30E-06</td></tr><tr><td rowspan="2" align="left" valign="middle" colspan="1">6</td><td rowspan="2" align="left" valign="middle" colspan="1">rs2798641(109374743), ARMC2(intron)</td><td rowspan="2" align="left" valign="middle" colspan="1">T</td><td align="left" valign="middle" rowspan="1" colspan="1">FEV<sub>1</sub>/FVC</td><td align="left" valign="middle" rowspan="1" colspan="1">−0.047 (0.009)</td><td align="left" valign="middle" rowspan="1" colspan="1">2.81E-07</td><td rowspan="2" align="left" valign="middle" colspan="1">0.183</td><td rowspan="2" align="left" valign="middle" colspan="1">46369</td><td align="left" valign="middle" rowspan="1" colspan="1">−0.03 (0.012)</td><td align="left" valign="middle" rowspan="1" colspan="1">1.57E-02</td><td rowspan="2" align="left" valign="middle" colspan="1">0.179</td><td rowspan="2" align="left" valign="middle" colspan="1">21173</td><td align="left" valign="middle" rowspan="1" colspan="1">−0.041 (0.007)</td><td align="left" valign="middle" rowspan="1" colspan="1">8.35E-09</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">FEV<sub>1</sub></td><td align="left" valign="middle" rowspan="1" colspan="1">−0.046 (0.009)</td><td align="left" valign="middle" rowspan="1" colspan="1">5.39E-07</td><td align="left" valign="middle" rowspan="1" colspan="1">−0.009 (0.01)</td><td align="left" valign="middle" rowspan="1" colspan="1">3.35E-01</td><td align="left" valign="middle" rowspan="1" colspan="1">−0.03 (0.006)</td><td align="left" valign="middle" rowspan="1" colspan="1">4.69E-06</td></tr><tr><td rowspan="2" align="left" valign="middle" colspan="1">10</td><td rowspan="2" align="left" valign="middle" colspan="1">rs7068966(12317998), CDC123(intron)</td><td rowspan="2" align="left" valign="middle" colspan="1">T</td><td align="left" valign="middle" rowspan="1" colspan="1">FEV<sub>1</sub>/FVC</td><td align="left" valign="middle" rowspan="1" colspan="1">0.045 (0.007)</td><td align="left" valign="middle" rowspan="1" colspan="1">1.28E-10</td><td rowspan="2" align="left" valign="middle" colspan="1">0.519</td><td rowspan="2" align="left" valign="middle" colspan="1">47085</td><td align="left" valign="middle" rowspan="1" colspan="1">0.023 (0.006)</td><td align="left" valign="middle" rowspan="1" colspan="1">3.86E-04</td><td rowspan="2" align="left" valign="middle" colspan="1">0.518</td><td rowspan="2" align="left" valign="middle" colspan="1">46067</td><td align="left" valign="middle" rowspan="1" colspan="1">0.033 (0.005)</td><td align="left" valign="middle" rowspan="1" colspan="1">6.13E-13</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">FEV<sub>1</sub></td><td align="left" valign="middle" rowspan="1" colspan="1">0.04 (0.007)</td><td align="left" valign="middle" rowspan="1" colspan="1">1.19E-08</td><td align="left" valign="middle" rowspan="1" colspan="1">0.022 (0.005)</td><td align="left" valign="middle" rowspan="1" colspan="1">3.56E-05</td><td align="left" valign="middle" rowspan="1" colspan="1">0.029 (0.004)</td><td align="left" valign="middle" rowspan="1" colspan="1">2.82E-12</td></tr><tr><td rowspan="2" align="left" valign="middle" colspan="1">10</td><td rowspan="2" align="left" valign="middle" colspan="1">rs11001819(77985230), C10orf11(intron)</td><td rowspan="2" align="left" valign="middle" colspan="1">G</td><td align="left" valign="middle" rowspan="1" colspan="1">FEV<sub>1</sub>/FVC</td><td align="left" valign="middle" rowspan="1" colspan="1">−0.019 (0.007)</td><td align="left" valign="middle" rowspan="1" colspan="1">6.50E-03</td><td rowspan="2" align="left" valign="middle" colspan="1">0.522</td><td rowspan="2" align="left" valign="middle" colspan="1">45546</td><td align="left" valign="middle" rowspan="1" colspan="1">−0.006 (0.006)</td><td align="left" valign="middle" rowspan="1" colspan="1">3.17E-01</td><td rowspan="2" align="left" valign="middle" colspan="1">0.506</td><td rowspan="2" align="left" valign="middle" colspan="1">45932</td><td align="left" valign="middle" rowspan="1" colspan="1">−0.012 (0.005)</td><td align="left" valign="middle" rowspan="1" colspan="1">7.58E-03</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">FEV<sub>1</sub></td><td align="left" valign="middle" rowspan="1" colspan="1">−0.041 (0.007)</td><td align="left" valign="middle" rowspan="1" colspan="1">1.42E-08</td><td align="left" valign="middle" rowspan="1" colspan="1">−0.022 (0.005)</td><td align="left" valign="middle" rowspan="1" colspan="1">3.10E-05</td><td align="left" valign="middle" rowspan="1" colspan="1">−0.029 (0.004)</td><td align="left" valign="middle" rowspan="1" colspan="1">2.98E-12</td></tr><tr><td rowspan="2" align="left" valign="middle" colspan="1">12</td><td rowspan="2" align="left" valign="middle" colspan="1">rs11172113(55813550), LRP1(intron)</td><td rowspan="2" align="left" valign="middle" colspan="1">T</td><td align="left" valign="middle" rowspan="1" colspan="1">FEV<sub>1</sub>/FVC</td><td align="left" valign="middle" rowspan="1" colspan="1">−0.035 (0.007)</td><td align="left" valign="middle" rowspan="1" colspan="1">1.36E-06</td><td rowspan="2" align="left" valign="middle" colspan="1">0.607</td><td rowspan="2" align="left" valign="middle" colspan="1">45387</td><td align="left" valign="middle" rowspan="1" colspan="1">−0.026 (0.01)</td><td align="left" valign="middle" rowspan="1" colspan="1">5.83E-03</td><td rowspan="2" align="left" valign="middle" colspan="1">0.59</td><td rowspan="2" align="left" valign="middle" colspan="1">20509</td><td align="left" valign="middle" rowspan="1" colspan="1">−0.032 (0.006)</td><td align="left" valign="middle" rowspan="1" colspan="1">1.24E-08</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">FEV<sub>1</sub></td><td align="left" valign="middle" rowspan="1" colspan="1">−0.021 (0.007)</td><td align="left" valign="middle" rowspan="1" colspan="1">3.55E-03</td><td align="left" valign="middle" rowspan="1" colspan="1">−0.003 (0.007)</td><td align="left" valign="middle" rowspan="1" colspan="1">6.94E-01</td><td align="left" valign="middle" rowspan="1" colspan="1">−0.013 (0.005)</td><td align="left" valign="middle" rowspan="1" colspan="1">1.19E-02</td></tr><tr><td rowspan="2" align="left" valign="middle" colspan="1">12</td><td rowspan="2" align="left" valign="middle" colspan="1">rs1036429(94795559), CCDC38(intron)</td><td rowspan="2" align="left" valign="middle" colspan="1">T</td><td align="left" valign="middle" rowspan="1" colspan="1">FEV<sub>1</sub>/FVC</td><td align="left" valign="middle" rowspan="1" colspan="1">0.049 (0.008)</td><td align="left" valign="middle" rowspan="1" colspan="1">1.24E-08</td><td rowspan="2" align="left" valign="middle" colspan="1">0.2</td><td rowspan="2" align="left" valign="middle" colspan="1">47814</td><td align="left" valign="middle" rowspan="1" colspan="1">0.028 (0.008)</td><td align="left" valign="middle" rowspan="1" colspan="1">3.35E-04</td><td rowspan="2" align="left" valign="middle" colspan="1">0.214</td><td rowspan="2" align="left" valign="middle" colspan="1">46311</td><td align="left" valign="middle" rowspan="1" colspan="1">0.038 (0.006)</td><td align="left" valign="middle" rowspan="1" colspan="1">2.30E-11</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">FEV<sub>1</sub></td><td align="left" valign="middle" rowspan="1" colspan="1">0.01 (0.008)</td><td align="left" valign="middle" rowspan="1" colspan="1">2.67E-01</td><td align="left" valign="middle" rowspan="1" colspan="1">0.004 (0.006)</td><td align="left" valign="middle" rowspan="1" colspan="1">5.38E-01</td><td align="left" valign="middle" rowspan="1" colspan="1">0.006 (0.005)</td><td align="left" valign="middle" rowspan="1" colspan="1">2.26E-01</td></tr><tr><td rowspan="2" align="left" valign="middle" colspan="1">16</td><td rowspan="2" align="left" valign="middle" colspan="1">rs12447804(56632783), MMP15(intron)</td><td rowspan="2" align="left" valign="middle" colspan="1">T</td><td align="left" valign="middle" rowspan="1" colspan="1">FEV<sub>1</sub>/FVC</td><td align="left" valign="middle" rowspan="1" colspan="1">−0.053 (0.009)</td><td align="left" valign="middle" rowspan="1" colspan="1">7.12E-08</td><td rowspan="2" align="left" valign="middle" colspan="1">0.208</td><td rowspan="2" align="left" valign="middle" colspan="1">35123</td><td align="left" valign="middle" rowspan="1" colspan="1">−0.021 (0.01)</td><td align="left" valign="middle" rowspan="1" colspan="1">4.20E-02</td><td rowspan="2" align="left" valign="middle" colspan="1">0.222</td><td rowspan="2" align="left" valign="middle" colspan="1">24398</td><td align="left" valign="middle" rowspan="1" colspan="1">−0.038 (0.007)</td><td align="left" valign="middle" rowspan="1" colspan="1">3.59E-08</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">FEV<sub>1</sub></td><td align="left" valign="middle" rowspan="1" colspan="1">−0.017 (0.009)</td><td align="left" valign="middle" rowspan="1" colspan="1">8.02E-02</td><td align="left" valign="middle" rowspan="1" colspan="1">0.004 (0.007)</td><td align="left" valign="middle" rowspan="1" colspan="1">5.71E-01</td><td align="left" valign="middle" rowspan="1" colspan="1">−0.004 (0.006)</td><td align="left" valign="middle" rowspan="1" colspan="1">4.73E-01</td></tr><tr><td rowspan="2" align="left" valign="middle" colspan="1">16</td><td rowspan="2" align="left" valign="middle" colspan="1">rs2865531(73947817), CFDP1(intron)</td><td rowspan="2" align="left" valign="middle" colspan="1">T</td><td align="left" valign="middle" rowspan="1" colspan="1">FEV<sub>1</sub>/FVC</td><td align="left" valign="middle" rowspan="1" colspan="1">0.039 (0.007)</td><td align="left" valign="middle" rowspan="1" colspan="1">2.30E-08</td><td rowspan="2" align="left" valign="middle" colspan="1">0.418</td><td rowspan="2" align="left" valign="middle" colspan="1">47594</td><td align="left" valign="middle" rowspan="1" colspan="1">0.024 (0.006)</td><td align="left" valign="middle" rowspan="1" colspan="1">1.94E-04</td><td rowspan="2" align="left" valign="middle" colspan="1">0.409</td><td rowspan="2" align="left" valign="middle" colspan="1">46304</td><td align="left" valign="middle" rowspan="1" colspan="1">0.031 (0.005)</td><td align="left" valign="middle" rowspan="1" colspan="1">1.77E-11</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">FEV<sub>1</sub></td><td align="left" valign="middle" rowspan="1" colspan="1">0.024 (0.007)</td><td align="left" valign="middle" rowspan="1" colspan="1">6.30E-04</td><td align="left" valign="middle" rowspan="1" colspan="1">0.011 (0.005)</td><td align="left" valign="middle" rowspan="1" colspan="1">3.89E-02</td><td align="left" valign="middle" rowspan="1" colspan="1">0.016 (0.004)</td><td align="left" valign="middle" rowspan="1" colspan="1">1.09E-04</td></tr><tr><td rowspan="2" align="left" valign="middle" colspan="1">21</td><td rowspan="2" align="left" valign="middle" colspan="1">rs9978142(34574109), KCNE2(upstream)</td><td rowspan="2" align="left" valign="middle" colspan="1">T</td><td align="left" valign="middle" rowspan="1" colspan="1">FEV<sub>1</sub>/FVC</td><td align="left" valign="middle" rowspan="1" colspan="1">−0.048 (0.009)</td><td align="left" valign="middle" rowspan="1" colspan="1">8.23E-07</td><td rowspan="2" align="left" valign="middle" colspan="1">0.156</td><td rowspan="2" align="left" valign="middle" colspan="1">44577</td><td align="left" valign="middle" rowspan="1" colspan="1">−0.031 (0.013)</td><td align="left" valign="middle" rowspan="1" colspan="1">1.75E-02</td><td rowspan="2" align="left" valign="middle" colspan="1">0.149</td><td rowspan="2" align="left" valign="middle" colspan="1">20944</td><td align="left" valign="middle" rowspan="1" colspan="1">−0.043 (0.008)</td><td align="left" valign="middle" rowspan="1" colspan="1">2.65E-08</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">FEV<sub>1</sub></td><td align="left" valign="middle" rowspan="1" colspan="1">−0.012 (0.009)</td><td align="left" valign="middle" rowspan="1" colspan="1">2.47E-01</td><td align="left" valign="middle" rowspan="1" colspan="1">−0.015 (0.01)</td><td align="left" valign="middle" rowspan="1" colspan="1">1.35E-01</td><td align="left" valign="middle" rowspan="1" colspan="1">−0.013 (0.007)</td><td align="left" valign="middle" rowspan="1" colspan="1">5.57E-02</td></tr></tbody></table></table-wrap><table-wrap id="T2" position="float" orientation="landscape"><label>Table 2</label><caption><p>Expression profiling of candidate genes in the lung and periphery. (+) indicates the gene is expressed in the cell type used and (−) indicates the gene expression at mRNA level is not detected following 40 cycles of PCR. PCR profiling of gene transcripts in the human lung demonstrates expression of all candidates except <italic>CCDC38</italic>, for which two sets of primers were designed and tested under different optimization conditions. None of these assays detected expression of <italic>CCDC38</italic> in the cell types analysed. The <italic>SNRPF</italic> gene neighbouring <italic>CCDC38</italic> and harbouring SNPs with strong LD with <italic>CCDC38</italic>’s sentinel SNP was assayed instead. All PCR products were sequence verified. Glyceraldehyde-3-phosphate dehydrogenase gene (<italic>GAPDH</italic>) was used as a positive control for the cDNA and was expressed in all tissues. HASM: Human airway smooth muscle. HBEC: Human bronchial epithelial cells. PBMC: peripheral blood mononuclear cells.</p></caption><table frame="box" rules="all"><thead><tr><th rowspan="2" align="left" valign="bottom" colspan="1">Sentinel SNP<break></break>(relationship<break></break>to gene)</th><th rowspan="2" align="left" valign="bottom" colspan="1">Chr.</th><th rowspan="2" align="left" valign="bottom" colspan="1">Gene</th><th rowspan="2" align="left" valign="bottom" colspan="1">Putative Function of encoded<break></break>protein</th><th colspan="4" align="left" valign="bottom" rowspan="1">Tissue</th></tr><tr><th align="left" valign="bottom" rowspan="1" colspan="1">Lung</th><th align="left" valign="bottom" rowspan="1" colspan="1">HASM</th><th align="left" valign="bottom" rowspan="1" colspan="1">HBEC</th><th align="left" valign="bottom" rowspan="1" colspan="1">PBMC</th></tr></thead><tbody><tr><td align="left" valign="bottom" rowspan="1" colspan="1">rs993925<break></break>(intron)</td><td align="left" valign="bottom" rowspan="1" colspan="1">1</td><td align="left" valign="bottom" rowspan="1" colspan="1"><bold><italic>TGFB2</italic></bold></td><td align="left" valign="bottom" rowspan="1" colspan="1">Cytokine with roles in pro-fibrotic<break></break>cytokine modulating epithelial repair<break></break>mechanisms and extracellular matrix<break></break>homeostasis including collagen<break></break>deposition<sup><xref rid="R40" ref-type="bibr">40</xref></sup></td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td><td align="left" valign="bottom" rowspan="1" colspan="1">−
</td><td align="left" valign="bottom" rowspan="1" colspan="1">−
</td></tr><tr><td align="left" valign="bottom" rowspan="1" colspan="1">rs2284746<break></break>(intron)</td><td align="left" valign="bottom" rowspan="1" colspan="1">1</td><td align="left" valign="bottom" rowspan="1" colspan="1"><bold><italic>MFAP2</italic></bold></td><td align="left" valign="bottom" rowspan="1" colspan="1">Major antigen of elastin-associated<break></break>microfibrils17 and a candidate for<break></break>involvement in the etiology of inherited<break></break>connective tissue diseases.</td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td><td align="left" valign="bottom" rowspan="1" colspan="1">−
</td></tr><tr><td align="left" valign="bottom" rowspan="1" colspan="1">rs12477314<break></break>(downstream)</td><td align="left" valign="bottom" rowspan="1" colspan="1">2</td><td align="left" valign="bottom" rowspan="1" colspan="1"><bold><italic>HDAC4</italic></bold></td><td align="left" valign="bottom" rowspan="1" colspan="1">Deacetylase of histone surrounding DNA<break></break>thus influencing transcription factor<break></break>access to the DNA possibly repressing<break></break>gene transcription.</td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td></tr><tr><td align="left" valign="bottom" rowspan="1" colspan="1">rs1344555<break></break>(intron)</td><td align="left" valign="bottom" rowspan="1" colspan="1">3</td><td align="left" valign="bottom" rowspan="1" colspan="1"><bold><italic>EVI1</italic></bold></td><td align="left" valign="bottom" rowspan="1" colspan="1">Zinc finger transcription factor, encoded<break></break>as part of MDS1/EVI1 complex locus<break></break>(MECOM).</td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td><td align="left" valign="bottom" rowspan="1" colspan="1">−
</td></tr><tr><td align="left" valign="bottom" rowspan="1" colspan="1">rs1529672<break></break>(intron)</td><td align="left" valign="bottom" rowspan="1" colspan="1">3</td><td align="left" valign="bottom" rowspan="1" colspan="1"><bold><italic>RARB</italic></bold></td><td align="left" valign="bottom" rowspan="1" colspan="1">Nuclear retinoic acid receptor responsive<break></break>to retinoic acid, a vitamin A derivative<break></break>and which also controls cell proliferation<break></break>and differentiation.</td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td></tr><tr><td align="left" valign="bottom" rowspan="1" colspan="1">rs153916<break></break>(intron)</td><td align="left" valign="bottom" rowspan="1" colspan="1">5</td><td align="left" valign="bottom" rowspan="1" colspan="1"><bold><italic>SPATA9</italic></bold></td><td align="left" valign="bottom" rowspan="1" colspan="1">Initially identified as a mediator of<break></break>spermatogenesis, other family members<break></break>may have a role in pancreatic<break></break>development and β-cell proliferation<sup><xref rid="R41" ref-type="bibr">41</xref></sup></td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td></tr><tr><td align="left" valign="bottom" rowspan="1" colspan="1">rs2798641<break></break>(intron)</td><td align="left" valign="bottom" rowspan="1" colspan="1">6</td><td align="left" valign="bottom" rowspan="1" colspan="1"><bold><italic>ARMC2</italic></bold></td><td align="left" valign="bottom" rowspan="1" colspan="1">Function unknown although other family<break></break>members have been identified as having<break></break>roles in cell signalling, protein<break></break>degradation and cytoskeleton functions<sup><xref rid="R42" ref-type="bibr">42</xref></sup></td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td></tr><tr><td align="left" valign="bottom" rowspan="1" colspan="1">rs2857595<break></break>(upstream)</td><td align="left" valign="bottom" rowspan="1" colspan="1">6</td><td align="left" valign="bottom" rowspan="1" colspan="1"><bold><italic>NCR3</italic></bold></td><td align="left" valign="bottom" rowspan="1" colspan="1">Required for efficient cytotoxicity<break></break>responses by natural killer cells against<break></break>normal cells and tumours<sup><xref rid="R43" ref-type="bibr">43</xref></sup></td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td><td align="left" valign="bottom" rowspan="1" colspan="1">−
</td><td align="left" valign="bottom" rowspan="1" colspan="1">−
</td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td></tr><tr><td align="left" valign="bottom" rowspan="1" colspan="1">rs6903823<break></break>(intron)</td><td align="left" valign="bottom" rowspan="1" colspan="1">6</td><td align="left" valign="bottom" rowspan="1" colspan="1"><bold><italic>ZKSCAN3</italic></bold></td><td align="left" valign="bottom" rowspan="1" colspan="1">Transcription factor involved in cell<break></break>growth/cell cycle/signal transduction</td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td></tr><tr><td align="left" valign="bottom" rowspan="1" colspan="1">rs7068966<break></break>(intron)</td><td align="left" valign="bottom" rowspan="1" colspan="1">10</td><td align="left" valign="bottom" rowspan="1" colspan="1"><bold><italic>CDC123</italic></bold></td><td align="left" valign="bottom" rowspan="1" colspan="1">Homologue in yeast shown to be a<break></break>critical control protein modulating<break></break>Eukaryotic initiation factor 2 in times of<break></break>cell stress</td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td></tr><tr><td align="left" valign="bottom" rowspan="1" colspan="1">rs11001819<break></break>(intron)</td><td align="left" valign="bottom" rowspan="1" colspan="1">10</td><td align="left" valign="bottom" rowspan="1" colspan="1"><bold><italic>C10orf11</italic></bold></td><td align="left" valign="bottom" rowspan="1" colspan="1">Function unknown</td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td></tr><tr><td align="left" valign="bottom" rowspan="1" colspan="1">rs11172113<break></break>(intron)</td><td align="left" valign="bottom" rowspan="1" colspan="1">12</td><td align="left" valign="bottom" rowspan="1" colspan="1"><bold><italic>LRP1</italic></bold></td><td align="left" valign="bottom" rowspan="1" colspan="1">Potentially diverse roles including cell<break></break>signalling and migration<sup><xref rid="R44" ref-type="bibr">44</xref></sup></td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td></tr><tr><td align="left" valign="bottom" rowspan="1" colspan="1">rs1036429<break></break>(intron)</td><td align="left" valign="bottom" rowspan="1" colspan="1">12</td><td align="left" valign="bottom" rowspan="1" colspan="1"><bold><italic>CCDC38</italic></bold></td><td align="left" valign="bottom" rowspan="1" colspan="1">Function unknown although other family<break></break>members involved in a diverse array of<break></break>functions skeletal and motor function<sup><xref rid="R45" ref-type="bibr">45</xref></sup></td><td align="left" valign="bottom" rowspan="1" colspan="1">−
</td><td align="left" valign="bottom" rowspan="1" colspan="1">−
</td><td align="left" valign="bottom" rowspan="1" colspan="1">−
</td><td align="left" valign="bottom" rowspan="1" colspan="1">−
</td></tr><tr><td align="left" valign="bottom" rowspan="1" colspan="1">rs1036429<break></break>(r<sup>2</sup>=0.96 with<break></break>rs4762633 in<break></break>SNRPF)</td><td align="left" valign="bottom" rowspan="1" colspan="1">12</td><td align="left" valign="bottom" rowspan="1" colspan="1"><bold><italic>SNRPF</italic></bold></td><td align="left" valign="bottom" rowspan="1" colspan="1">Small nuclear ribonucleoprotein F</td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td></tr><tr><td align="left" valign="bottom" rowspan="1" colspan="1">rs12447804<break></break>(intron)</td><td align="left" valign="bottom" rowspan="1" colspan="1">16</td><td align="left" valign="bottom" rowspan="1" colspan="1"><bold><italic>MMP15</italic></bold></td><td align="left" valign="bottom" rowspan="1" colspan="1">Member of a large protease family with<break></break>diverse functional roles via protease<break></break>activity and specificity including; tissue<break></break>remodelling, wound healing,<break></break>angiogenesis, and tumor invasion.</td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td><td align="left" valign="bottom" rowspan="1" colspan="1">−
</td></tr><tr><td align="left" valign="bottom" rowspan="1" colspan="1">rs2865531<break></break>(intron)</td><td align="left" valign="bottom" rowspan="1" colspan="1">16</td><td align="left" valign="bottom" rowspan="1" colspan="1"><bold><italic>CFDP1</italic></bold></td><td align="left" valign="bottom" rowspan="1" colspan="1">Craniofacial Development Protein 1</td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td></tr><tr><td align="left" valign="bottom" rowspan="1" colspan="1">rs9978142<break></break>(upstream)</td><td align="left" valign="bottom" rowspan="1" colspan="1">21</td><td align="left" valign="bottom" rowspan="1" colspan="1"><bold><italic>KCNE2</italic></bold></td><td align="left" valign="bottom" rowspan="1" colspan="1">KCNQ1-KCNE2 K+ channels may<break></break>modulate transepithelial anion secretion<break></break>in Calu3 airway epithelial cells<sup><xref rid="R46" ref-type="bibr">46</xref></sup>.</td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td><td align="left" valign="bottom" rowspan="1" colspan="1">−
</td><td align="left" valign="bottom" rowspan="1" colspan="1">−
</td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td></tr><tr><td align="left" valign="bottom" rowspan="1" colspan="1"><bold>Reference</bold><break></break><bold>gene</bold></td><td align="left" valign="bottom" rowspan="1" colspan="1">12</td><td align="left" valign="bottom" rowspan="1" colspan="1"><bold><italic>GAPDH</italic></bold></td><td align="left" valign="bottom" rowspan="1" colspan="1"></td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td><td align="left" valign="bottom" rowspan="1" colspan="1">+</td></tr></tbody></table></table-wrap></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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