Genome-wide association analysis identifies six new loci associated with forced vital capacity

Daan W Loth; María Soler Artigas; Sina A Gharib; Louise V Wain; Nora Franceschini; Beate Koch; Tess D Pottinger; Albert Vernon Smith; Qing Duan; Chris Oldmeadow; Mi Kyeong Lee; David P Strachan; Alan L James; Jennifer E Huffman; Veronique Vitart; Adaikalavan Ramasamy; Nicholas J Wareham; Jaakko Kaprio; Xin-Qun Wang; Holly Trochet; Mika Kähönen; Claudia Flexeder; Eva Albrecht; Lorna M Lopez; Kim de Jong; Bharat Thyagarajan; Alexessander Couto Alves; Stefan Enroth; Ernst Omenaas; Peter K Joshi; Tove Fall; Ana Viñuela; Lenore J Launer; Laura R Loehr; Myriam Fornage; Guo Li; Jemma B Wilk; Wenbo Tang; Ani Manichaikul; Lies Lahousse; Tamara B Harris; Kari E North; Alicja R Rudnicka; Jennie Hui; Xiangjun Gu; Thomas Lumley; Alan F Wright; Nicholas D Hastie; Susan Campbell; Rajesh Kumar; Isabelle Pin; Robert A Scott; Kirsi H Pietiläinen; Ida Surakka; Yongmei Liu; Elizabeth G Holliday; Holger Schulz; Joachim Heinrich; Gail Davies; Judith M Vonk; Mary Wojczynski; Anneli Pouta; Asa Johansson; Sarah H Wild; Erik Ingelsson; Fernando Rivadeneira; Henry Völzke; Pirro G Hysi; Gudny Eiriksdottir; Alanna C Morrison; Jerome I Rotter; Wei Gao; Dirkje S Postma; Wendy B White; Stephen S Rich; Albert Hofman; Thor Aspelund; David Couper; Lewis J Smith; Bruce M Psaty; Kurt Lohman; Esteban G Burchard; André G Uitterlinden; Melissa Garcia; Bonnie R Joubert; Wendy L McArdle; A Bill Musk; Nadia Hansel; Susan R Heckbert; Lina Zgaga; Joyce B J van Meurs; Pau Navarro; Igor Rudan; Yeon-Mok Oh; Susan Redline; Deborah L Jarvis; Jing Hua Zhao; Taina Rantanen; George T O'Connor; Samuli Ripatti; Rodney J Scott; Stefan Karrasch; Harald Grallert; Nathan C Gaddis; John M Starr; Cisca Wijmenga; Ryan L Minster; David J Lederer; Juha Pekkanen; Ulf Gyllensten; Harry Campbell; Andrew P Morris; Sven Gläser; Christopher J Hammond; Kristin M Burkart; John Beilby; Stephen B Kritchevsky; Vilmundur Gudnason; Dana B Hancock; O Dale Williams; Ozren Polasek; Tatijana Zemunik; Ivana Kolcic; Marcy F Petrini; Matthias Wjst; Woo Jin Kim; David J Porteous; Generation Scotland; Blair H Smith; Anne Viljanen; Markku Heliövaara; John R Attia; Ian Sayers; Regina Hampel; Christian Gieger; Ian J Deary; H Marike Boezen; Anne Newman; Marjo-Riitta Jarvelin; James F Wilson; Lars Lind; Bruno H Stricker; Alexander Teumer; Timothy D Spector; Erik Melén; Marjolein J Peters; Leslie A Lange; R Graham Barr; Ken R Bracke; Fien M Verhamme; Joohon Sung; Pieter S Hiemstra; Patricia A Cassano; Akshay Sood; Caroline Hayward; Josée Dupuis; Ian P Hall; Guy G Brusselle; Martin D Tobin; Stephanie J London

doi:10.1038/ng.3011

Genome-wide association analysis identifies six new loci associated with forced vital capacity

Nat Genet. 2014 Jul;46(7):669-77. doi: 10.1038/ng.3011. Epub 2014 Jun 15.

Authors

Daan W Loth¹, María Soler Artigas², Sina A Gharib³, Louise V Wain², Nora Franceschini⁴, Beate Koch⁵, Tess D Pottinger⁶, Albert Vernon Smith⁷, Qing Duan⁸, Chris Oldmeadow⁹, Mi Kyeong Lee¹⁰, David P Strachan¹¹, Alan L James¹², Jennifer E Huffman¹³, Veronique Vitart¹³, Adaikalavan Ramasamy¹⁴, Nicholas J Wareham¹⁵, Jaakko Kaprio¹⁶, Xin-Qun Wang¹⁷, Holly Trochet¹³, Mika Kähönen¹⁸, Claudia Flexeder¹⁹, Eva Albrecht²⁰, Lorna M Lopez²¹, Kim de Jong²², Bharat Thyagarajan²³, Alexessander Couto Alves²⁴, Stefan Enroth²⁵, Ernst Omenaas²⁶, Peter K Joshi²⁷, Tove Fall²⁸, Ana Viñuela²⁹, Lenore J Launer³⁰, Laura R Loehr³¹, Myriam Fornage³², Guo Li³³, Jemma B Wilk³⁴, Wenbo Tang³⁵, Ani Manichaikul³⁶, Lies Lahousse³⁷, Tamara B Harris³⁰, Kari E North³⁸, Alicja R Rudnicka¹¹, Jennie Hui³⁹, Xiangjun Gu³², Thomas Lumley⁴⁰, Alan F Wright¹³, Nicholas D Hastie¹³, Susan Campbell¹³, Rajesh Kumar⁴¹, Isabelle Pin⁴², Robert A Scott¹⁵, Kirsi H Pietiläinen⁴³, Ida Surakka⁴⁴, Yongmei Liu⁴⁵, Elizabeth G Holliday⁹, Holger Schulz¹⁹, Joachim Heinrich⁴⁶, Gail Davies⁴⁷, Judith M Vonk²², Mary Wojczynski⁴⁸, Anneli Pouta⁴⁹, Asa Johansson⁵⁰, Sarah H Wild²⁷, Erik Ingelsson⁵¹, Fernando Rivadeneira⁵², Henry Völzke⁵³, Pirro G Hysi²⁹, Gudny Eiriksdottir⁵⁴, Alanna C Morrison⁵⁵, Jerome I Rotter⁵⁶, Wei Gao⁵⁷, Dirkje S Postma⁵⁸, Wendy B White⁵⁹, Stephen S Rich⁶⁰, Albert Hofman⁶¹, Thor Aspelund⁶², David Couper⁶³, Lewis J Smith⁴¹, Bruce M Psaty⁶⁴, Kurt Lohman⁶⁵, Esteban G Burchard⁶⁶, André G Uitterlinden⁶⁷, Melissa Garcia³⁰, Bonnie R Joubert⁶⁸, Wendy L McArdle⁶⁹, A Bill Musk⁷⁰, Nadia Hansel⁷¹, Susan R Heckbert⁷², Lina Zgaga⁷³, Joyce B J van Meurs⁵², Pau Navarro¹³, Igor Rudan²⁷, Yeon-Mok Oh⁷⁴, Susan Redline⁷⁵, Deborah L Jarvis⁷⁶, Jing Hua Zhao¹⁵, Taina Rantanen⁷⁷, George T O'Connor⁷⁸, Samuli Ripatti⁷⁹, Rodney J Scott⁹, Stefan Karrasch⁸⁰, Harald Grallert⁸¹, Nathan C Gaddis⁸², John M Starr⁸³, Cisca Wijmenga⁸⁴, Ryan L Minster⁸⁵, David J Lederer⁸⁶, Juha Pekkanen⁸⁷, Ulf Gyllensten²⁵, Harry Campbell²⁷, Andrew P Morris⁸⁸, Sven Gläser⁸⁹, Christopher J Hammond²⁹, Kristin M Burkart⁹⁰, John Beilby³⁹, Stephen B Kritchevsky⁹¹, Vilmundur Gudnason⁶², Dana B Hancock⁹², O Dale Williams⁹³, Ozren Polasek⁹⁴, Tatijana Zemunik⁹⁵, Ivana Kolcic⁹⁴, Marcy F Petrini⁹⁶, Matthias Wjst⁹⁷, Woo Jin Kim⁹⁸, David J Porteous⁹⁹, Generation Scotland¹⁰⁰, Blair H Smith¹⁰¹, Anne Viljanen⁷⁷, Markku Heliövaara¹⁰², John R Attia⁹, Ian Sayers¹⁰³, Regina Hampel¹⁰⁴, Christian Gieger²⁰, Ian J Deary²¹, H Marike Boezen²², Anne Newman¹⁰⁵, Marjo-Riitta Jarvelin¹⁰⁶, James F Wilson²⁷, Lars Lind¹⁰⁷, Bruno H Stricker¹⁰⁸, Alexander Teumer¹⁰⁹, Timothy D Spector²⁹, Erik Melén¹¹⁰, Marjolein J Peters⁵², Leslie A Lange¹¹¹, R Graham Barr⁸⁶, Ken R Bracke¹¹², Fien M Verhamme¹¹², Joohon Sung¹¹³, Pieter S Hiemstra¹¹⁴, Patricia A Cassano¹¹⁵, Akshay Sood¹¹⁶, Caroline Hayward¹¹⁷, Josée Dupuis¹¹⁸, Ian P Hall¹¹⁹, Guy G Brusselle¹²⁰, Martin D Tobin², Stephanie J London¹²¹

Affiliations

¹ 1] Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands. [2] Netherlands Health Care Inspectorate, The Hague, the Netherlands. [3].
² 1] Genetic Epidemiology Group, Department of Health Sciences, University of Leicester, Leicester, UK. [2] National Institute for Health Research (NIHR) Leicester Respiratory Biomedical Research Unit, Glenfield Hospital, Leicester, UK. [3].
³ 1] Computational Medicine Core, Center for Lung Biology, University of Washington, Seattle, Washington, USA. [2] Department of Medicine, University of Washington, Seattle, Washington, USA. [3].
⁴ 1] Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. [2] Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. [3].
⁵ 1] Department of Internal Medicine B-Pneumology, Cardiology, Intensive Care and Infectious Diseases, University Hospital Greifswald, Greifswald, Germany. [2].
⁶ 1] Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York, USA. [2].
⁷ 1] Iceland Heart Association, Kopavogur, Iceland. [2] University of Iceland, Reykjavik, Iceland. [3].
⁸ 1] Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA. [2].
⁹ 1] Hunter Medical Research Institute, University of Newcastle, Newcastle, New South Wales, Australia. [2] Faculty of Health, University of Newcastle, Newcastle, New South Wales, Australia.
¹⁰ Institute of Health and Environment, Seoul National University, Seoul, South Korea.
¹¹ Division of Population Health Sciences and Education, St George's, University of London, London, UK.
¹² 1] Department of Pulmonary Physiology and Sleep Medicine/West Australian Sleep Disorders Research Institute, Nedlands, Western Australia, Australia. [2] School of Medicine and Pharmacology, The University of Western Australia, Perth, Western Australia, Australia. [3] Busselton Population Medical Research Institute, Busselton, Western Australia, Australia.
¹³ Medical Research Council (MRC) Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine (IGMM), University of Edinburgh, Edinburgh, UK.
¹⁴ 1] Respiratory Epidemiology and Public Health Group, National Heart and Lung Institute, Imperial College London, London, UK. [2] Department of Epidemiology and Biostatistics, MRC Health Protection Agency (HPA) Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.
¹⁵ MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.
¹⁶ 1] Hjelt Institute, Department of Public Health, University of Helsinki, Helsinki, Finland. [2] National Institute for Health and Welfare (THL), Helsinki, Finland. [3] Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
¹⁷ Division of Biostatistics and Epidemiology, Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia, USA.
¹⁸ Department of Clinical Physiology, University of Tampere and Tampere University Hospital, Tampere, Finland.
¹⁹ Institute of Epidemiology I, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
²⁰ Institute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
²¹ 1] Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK. [2] Department of Psychology, University of Edinburgh, Edinburgh, UK.
²² 1] Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. [2] Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
²³ Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, USA.
²⁴ Department of Epidemiology and Biostatistics, MRC Health Protection Agency (HPA) Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.
²⁵ 1] Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden. [2] Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
²⁶ 1] Centre for Clinical Research, Haukeland University Hospital, Bergen, Norway. [2] Department of Clinical Sciences, University of Bergen, Bergen, Norway.
²⁷ Centre for Population Health Sciences, Medical School, University of Edinburgh, Edinburgh, UK.
²⁸ 1] Science for Life Laboratory, Uppsala University, Uppsala, Sweden. [2] Molecular Epidemiology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
²⁹ Department of Twins Research and Genetic Epidemiology, King's College London, London, UK.
³⁰ Laboratory of Epidemiology, Demography and Biometry, National Institute on Aging, US National Institutes of Health, Bethesda, Maryland, USA.
³¹ 1] Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. [2] Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
³² 1] Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas, USA. [2] Human Genetics Center, University of Texas Health Science Center at Houston, Houston, Texas, USA.
³³ Cardiovascular Health Research Unit, University of Washington, Seattle, Washington, USA.
³⁴ Precision Medicine, Pfizer Global Research and Development, Cambridge, Massachusetts, USA.
³⁵ Division of Nutritional Sciences, Cornell University, Ithaca, New York, USA.
³⁶ 1] Division of Biostatistics and Epidemiology, Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia, USA. [2] Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, USA.
³⁷ 1] Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands. [2] Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
³⁸ Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
³⁹ PathWest Laboratory Medicine Washington, Nedlands, Western Australia, Australia.
⁴⁰ Department of Statistics, University of Auckland, Auckland, New Zealand.
⁴¹ Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
⁴² 1] Centre Hospitalier Universitaire de Grenoble, Grenoble, France. [2] INSERM U823, Institut Albert Bonniot, Grenoble, France. [3] Université Joseph Fourier, Grenoble, France.
⁴³ 1] Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland. [2] Obesity Research Unit, Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland. [3] Division of Internal Medicine, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland.
⁴⁴ 1] Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland. [2] Public Health Genomics Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare (THL), Helsinki, Finland.
⁴⁵ Department of Epidemiology and Prevention, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
⁴⁶ 1] Institute of Epidemiology I, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany. [2] Comprehensive Pneumology Center Munich (CPC-M), member of the German Center for Lung Research, Munich, Germany.
⁴⁷ 1] Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK. [2] Department of Psychology, University of Edinburgh, Edinburgh, UK. [3] Medical Genetics Section, Centre for Genomics and Experimental Medicine, MRC IGMM, University of Edinburgh, Edinburgh, UK. [4] MRC Institute of Genetics and Molecular Medicine, Edinburgh, UK.
⁴⁸ Department of Statistical Genomics, Washington University, St. Louis, Missouri, USA.
⁴⁹ 1] National Institute for Health and Welfare, Oulu, Finland. [2] Department of Clinical Sciences/Obstetrics and Gynecology, University Hospital of Oulu, University of Oulu, Oulu, Finland.
⁵⁰ 1] Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden. [2] Science for Life Laboratory, Uppsala University, Uppsala, Sweden. [3] Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
⁵¹ 1] Science for Life Laboratory, Uppsala University, Uppsala, Sweden. [2] Molecular Epidemiology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden. [3] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
⁵² 1] Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands. [2] Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), Rotterdam, the Netherlands.
⁵³ Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
⁵⁴ Iceland Heart Association, Kopavogur, Iceland.
⁵⁵ School of Public Health, University of Texas Health Science Center at Houston, Houston, Texas, USA.
⁵⁶ 1] Biomedical Research Institute, Harbor-University of California, Los Angeles (UCLA) Medical Center, Torrance, California, USA. [2] Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, California, USA.
⁵⁷ Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA.
⁵⁸ 1] Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. [2] Department of Pulmonology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
⁵⁹ Tougaloo College, Jackson, Mississippi, USA.
⁶⁰ Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, USA.
⁶¹ 1] Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands. [2] Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), Rotterdam, the Netherlands.
⁶² 1] Iceland Heart Association, Kopavogur, Iceland. [2] University of Iceland, Reykjavik, Iceland.
⁶³ Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
⁶⁴ 1] Department of Medicine, University of Washington, Seattle, Washington, USA. [2] Cardiovascular Health Research Unit, University of Washington, Seattle, Washington, USA. [3] Department of Epidemiology, University of Washington, Seattle, Washington, USA. [4] Group Health Research Institute, Group Health Cooperative, Seattle, Washington, USA.
⁶⁵ Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
⁶⁶ 1] Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California, USA. [2] Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
⁶⁷ 1] Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands. [2] Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands. [3] Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), Rotterdam, the Netherlands.
⁶⁸ Epidemiology Branch, National Institute of Environmental Health Sciences, US National Institutes of Health, US Department of Health and Human Services, Research Triangle Park, North Carolina, USA.
⁶⁹ School of Social and Community Medicine, University of Bristol, Bristol, UK.
⁷⁰ Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.
⁷¹ Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
⁷² 1] Cardiovascular Health Research Unit, University of Washington, Seattle, Washington, USA. [2] Department of Epidemiology, University of Washington, Seattle, Washington, USA. [3] Group Health Research Institute, Group Health Cooperative, Seattle, Washington, USA.
⁷³ 1] Department of Public Health and Primary Care, Trinity College Dublin, Dublin, Ireland. [2] Adrija Stampar School of Public Health, Medical School, University of Zagreb, Zagreb, Croatia.
⁷⁴ 1] Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. [2] Clinical Research Center for Chronic Obstructive Airway Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
⁷⁵ Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
⁷⁶ 1] Respiratory Epidemiology and Public Health Group, National Heart and Lung Institute, Imperial College London, London, UK. [2] MRC-PHE Centre for Environment and Health, Imperial College London, London, UK.
⁷⁷ Gerontology Research Centre, Department of Health Sciences, University of Jyväskylä, Jyväskylä, Finland.
⁷⁸ 1] Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts, USA. [2] National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, USA.
⁷⁹ 1] Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland. [2] Public Health Genomics Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare (THL), Helsinki, Finland. [3] Genetic Epidemiology Group, Wellcome Trust Sanger Institute, Hinxton, UK.
⁸⁰ 1] Institute of Epidemiology I, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany. [2] Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, Ludwig Maximilians Universität, Munich, Germany. [3] Institute of General Practice, University Hospital Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.
⁸¹ Research Unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
⁸² Research Computing Division, Research Triangle Institute International, Research Triangle Park, North Carolina, USA.
⁸³ 1] Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK. [2] Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, UK.
⁸⁴ Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
⁸⁵ Department of Human Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
⁸⁶ 1] Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York, USA. [2] Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, USA.
⁸⁷ 1] Department of Environmental Health, National Institute for Health and Welfare (THL), Kuopio, Finland. [2] Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
⁸⁸ Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
⁸⁹ Department of Internal Medicine B-Pneumology, Cardiology, Intensive Care and Infectious Diseases, University Hospital Greifswald, Greifswald, Germany.
⁹⁰ Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York, USA.
⁹¹ Sticht Center on Aging, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
⁹² 1] Epidemiology Branch, National Institute of Environmental Health Sciences, US National Institutes of Health, US Department of Health and Human Services, Research Triangle Park, North Carolina, USA. [2] Behavioral Health Epidemiology Program, Research Triangle Institute International, Research Triangle Park, North Carolina, USA.
⁹³ Florida International University, Miami, Florida, USA.
⁹⁴ Department of Public Health, Medical School, University of Split, Split, Croatia.
⁹⁵ Department of Medical Biology, Medical School, University of Split, Split, Croatia.
⁹⁶ Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, USA.
⁹⁷ Comprehensive Pneumology Center (CPC), Helmholtz Zentrum München (HMGU), Munich, Germany.
⁹⁸ 1] Department of Internal Medicine, Kangwon National University Hospital, School of Medicine, Kangwon National University, Chuncheon, South Korea. [2] Environmental Health Center, Kangwon National University Hospital, School of Medicine, Kangwon National University, Chuncheon, South Korea.
⁹⁹ Medical Genetics Section, Centre for Genomics and Experimental Medicine, MRC IGMM, University of Edinburgh, Edinburgh, UK.
¹⁰⁰ A collaboration between the University Medical Schools and National Health Service (NHS) in Aberdeen, Dundee, Edinburgh and Glasgow, UK.
¹⁰¹ Medical Research Institute, University of Dundee, Dundee, UK.
¹⁰² National Institute for Health and Welfare (THL), Helsinki, Finland.
¹⁰³ Division of Therapeutics and Molecular Medicine, University of Nottingham, Nottingham, UK.
¹⁰⁴ Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
¹⁰⁵ Department of Epidemiology, Center for Aging and Population Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
¹⁰⁶ 1] Department of Epidemiology and Biostatistics, MRC Health Protection Agency (HPA) Centre for Environment and Health, School of Public Health, Imperial College London, London, UK. [2] Institute of Health Sciences, University of Oulu, Oulu, Finland. [3] Biocenter Oulu, University of Oulu, Oulu, Finland. [4] Unit of Primary Care, Oulu University Hospital, Oulu, Finland. [5] Department of Children and Young People and Families, National Institute for Health and Welfare, Oulu, Finland.
¹⁰⁷ Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
¹⁰⁸ 1] Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands. [2] Netherlands Health Care Inspectorate, The Hague, the Netherlands. [3] Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands. [4] Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), Rotterdam, the Netherlands.
¹⁰⁹ Department for Genetics and Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
¹¹⁰ Institute of Environmental Medicine, Karolinska Institutet and Sachs' Children's Hospital, Stockholm, Sweden.
¹¹¹ Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA.
¹¹² Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
¹¹³ 1] Institute of Health and Environment, Seoul National University, Seoul, South Korea. [2] Complex Disease and Genetic Epidemiology Branch, Department of Epidemiology, Seoul National University School of Public Health, Seoul, South Korea.
¹¹⁴ Department of Pulmonology, Leiden University Medical Center, Leiden, the Netherlands.
¹¹⁵ 1] Division of Nutritional Sciences, Cornell University, Ithaca, New York, USA. [2] Department of Public Health, Division of Biostatistics and Epidemiology, Weill Cornell Medical College, New York, New York, USA.
¹¹⁶ 1] University of New Mexico Health Sciences Center School of Medicine, Albuquerque, New Mexico, USA. [2].
¹¹⁷ 1] Medical Research Council (MRC) Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine (IGMM), University of Edinburgh, Edinburgh, UK. [2].
¹¹⁸ 1] Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA. [2] National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, USA. [3].
¹¹⁹ 1] Division of Therapeutics and Molecular Medicine, University of Nottingham, Nottingham, UK. [2].
¹²⁰ 1] Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands. [2] Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium. [3] Department of Respiratory Medicine, Erasmus MC, Rotterdam, the Netherlands. [4].
¹²¹ 1] Epidemiology Branch, National Institute of Environmental Health Sciences, US National Institutes of Health, US Department of Health and Human Services, Research Triangle Park, North Carolina, USA. [2].

PMID: 24929828
PMCID: PMC4140093
DOI: 10.1038/ng.3011

Abstract

Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10(-8)) with FVC in or near EFEMP1, BMP6, MIR129-2-HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease.

MeSH terms

Cohort Studies
Databases, Genetic
Follow-Up Studies
Forced Expiratory Volume
Genetic Loci / genetics*
Genetic Predisposition to Disease
Genome, Human*
Genome-Wide Association Study*
Humans
Lung Diseases / genetics*
Lung Diseases / pathology
Meta-Analysis as Topic
Polymorphism, Single Nucleotide / genetics
Prognosis
Quantitative Trait Loci / genetics
Respiratory Function Tests
Spirometry
Vital Capacity / genetics*

Associated data

GEO/GSE14334

Abstract

MeSH terms

Associated data

Grants and funding