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Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function

Nature Genetics volume 43, pages 1082–1090 (2011)Cite this article

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Abstract

Pulmonary function measures reflect respiratory health and are used in the diagnosis of chronic obstructive pulmonary disease. We tested genome-wide association with forced expiratory volume in 1 second and the ratio of forced expiratory volume in 1 second to forced vital capacity in 48,201 individuals of European ancestry with follow up of the top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P < 5 × 10−8) with pulmonary function in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (also known as EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1 and KCNE2. 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.

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Figure 1: Study design.
Figure 2: Manhattan plots of association results for FEV1/FVC and FEV1 (analysis stage 1).

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Acknowledgements

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.

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, partially 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 Institutes 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).

Author information

Author notes

  1. María Soler Artigas, Daan W Loth, Louise V Wain, Sina A Gharib, Ma'en Obeidat, Wenbo Tang, Bruno H Ch Stricker, Paul Elliott, George T O'Connor, David P Strachan, Stephanie J London, Ian P Hall, Vilmundur Gudnason and Martin D Tobin: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Health Sciences, University of Leicester, Leicester, UK

    María Soler Artigas, Louise V Wain & Martin D Tobin

  2. Department of Genetics, University of Leicester, Leicester, UK

    María Soler Artigas, Louise V Wain & Martin D Tobin

  3. Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands

    Daan W Loth, Mark Eijgelsheim, Albert Hofman, Fernando Rivadeneira, André G Uitterlinden & Bruno H Ch Stricker

  4. Inspectorate of Healthcare, The Hague, The Netherlands

    Daan W Loth & Bruno H Ch Stricker

  5. Center for Lung Biology, University of Washington, Seattle, Washington, USA

    Sina A Gharib

  6. Department of Medicine, University of Washington, Seattle, Washington, USA

    Sina A Gharib, Kristin D Marciante & Bruce M Psaty

  7. Division of Therapeutics and Molecular Medicine, Nottingham Respiratory Biomedical Research Unit, University Hospital of Nottingham, Nottingham, London, UK

    Ma'en Obeidat, Khalid A Al Balushi, John D Blakey, Amanda Henry, Ian Sayers & Ian P Hall

  8. Division of Nutritional Sciences, Cornell University Ithaca, New York, USA

    Wenbo Tang & Patricia A Cassano

  9. Department of Twin Research and Genetic Epidemiology, King's College London, London, UK

    Guangju Zhai, Christopher J Hammond, Pirro G Hysi, Massimo Mangino & Tim D Spector

  10. Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada

    Guangju Zhai

  11. Medical Research Council (MRC) Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK

    Jing Hua Zhao, Ruth J F Loos & Nicholas J Wareham

  12. Icelandic Heart Association, Kopavogur, Iceland

    Albert Vernon Smith, Thor Aspelund, Gudny Eiriksdottir, Gauti Kjartan Gislason & Vilmundur Gudnason

  13. University of Iceland, Reykjavik, Iceland

    Albert Vernon Smith, Thor Aspelund & Vilmundur Gudnason

  14. MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK

    Jennifer E Huffman, Veronique Vitart, Alan F Wright & Caroline Hayward

  15. Institute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany

    Eva Albrecht & Christian Gieger

  16. School of Medicine, University of St. Andrews, St. Andrews, Scotland, UK.,

    Catherine M Jackson

  17. MRC Centre for Causal Analyses in Translational Epidemiology, School of Social and Community Medicine, University of Bristol, Bristol, UK

    David M Evans, George Davey Smith & Debbie A Lawlor

  18. Genetic Epidemiology and Biostatistics Platform, Ontario Institute for Cancer Research, Toronto, Ontario, Canada

    Gemma Cadby & Lyle J Palmer

  19. Prosserman Centre for Health Research, Samuel Lunenfeld Research Institute, Toronto, Ontario, Canada

    Gemma Cadby, Lyle J Palmer & Nicole M Warrington

  20. Brown Foundation Institute of Molecular Medicine, University of Texas at Houston, Houston, Texas, USA

    Myriam Fornage & Xiangjun Gu

  21. Human Genetics Center, School of Public Health, University of Texas at Houston, Houston, Texas, USA

    Myriam Fornage & Alanna C Morrison

  22. Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, USA

    Ani Manichaikul & Stephen S Rich

  23. Department of Public Health Sciences, Division of Biostatistics and Epidemiology, University of Virginia, Charlottesville, Virginia, USA

    Ani Manichaikul

  24. Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, UK

    Lorna M Lopez, Ian J Deary, Sarah E Harris & John M Starr

  25. Department of Psychology, The University of Edinburgh, Edinburgh, UK

    Lorna M Lopez & Ian J Deary

  26. 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

    Toby Johnson

  27. Department of Thoracic Surgery, Vanderbilt University, Nashville, Tennessee, USA

    Melinda C Aldrich

  28. Division of Epidemiology, Vanderbilt University, Nashville, Tennessee, USA

    Melinda C Aldrich

  29. Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge, UK.,

    Inês Barroso & So-Youn Shin

  30. University of Cambridge Metabolic Research Labs, Institute of Metabolic Science Addenbrooke's Hospital, Cambridge, UK

    Inês Barroso

  31. Centre for Population Health Sciences, The University of Edinburgh, Edinburgh, UK

    Harry Campbell, Igor Rudan, Sarah H Wild, Lina Zgaga & James F Wilson

  32. Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, USA

    David J Couper

  33. Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, USA

    Nora Franceschini, Laura R Loehr & Kari E North

  34. Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA

    Melissa Garcia, Tamara B Harris & Lenore J Launer

  35. Croatian Centre for Global Health, The University of Split Medical School, Split, Croatia

    Ivica Grkovic, Stipan Jankovic & Igor Rudan

  36. Department of Health and Human Services, Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA

    Dana B Hancock, Bonnie R Joubert & Stephanie J London

  37. Behavioral Health Epidemiology Program, Research Triangle Institute International, Research Triangle Park, North Carolina, USA

    Dana B Hancock

  38. Respiratory Epidemiology and Public Health, Imperial College London, London, UK.,

    Adaikalavan Ramasamy & Deborah L Jarvis

  39. Department of Epidemiology and Biostatistics, Imperial College London, London, UK

    Adaikalavan Ramasamy, Marjo-Riitta Järvelin & Paul Elliott

  40. Department of Medical and Molecular Genetics, King's College London, Guy's Hospital, London, UK

    Adaikalavan Ramasamy

  41. Cardiovascular Health Research Unit, University of Washington, Seattle, Washington, USA

    Susan R Heckbert, Kristin D Marciante & Bruce M Psaty

  42. Department of Epidemiology, University of Washington, Seattle, Washington, USA

    Susan R Heckbert & Bruce M Psaty

  43. Group Health Research Institute, Group Health Cooperative, Seattle, Washington, USA

    Susan R Heckbert & Bruce M Psaty

  44. National Institute for Health and Welfare, Helsinki, Finland

    Markku Heliövaara & Jaakko Kaprio

  45. Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Greifswald, Germany

    Georg Homuth

  46. Department of Pulmonary Physiology and Sleep Medicine/West Australian Sleep Disorders Research Institute, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia

    Alan L James

  47. The School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia

    Alan L James & Arthur W Musk

  48. Department of Respiratory Medicine, Busselton Population Medical Research Foundation, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia

    Alan L James, Jennie Hui, Michael L Hunter & Arthur W Musk

  49. Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, Ludwig-Maximilians-University, Munich, Germany

    Stefan Karrasch

  50. Unit for Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany

    Norman Klopp

  51. Department of Internal Medicine B, University Hospital Greifswald, Greifswald, Germany

    Beate Koch

  52. Sticht Center on Aging, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA

    Stephen B Kritchevsky

  53. Epidemiology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA

    Yongmei Liu

  54. Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA

    Kurt Lohman

  55. Department of Statistics, University of Auckland, Auckland, New Zealand

    Thomas Lumley

  56. School of Women's and Infants' Health, The University of Western Australia, Perth, Western Australia, Australia

    Wei Q Ang, Nicole M Warrington & Craig E Pennell

  57. Department of Medicine, Columbia University Medical Center, New York, New York, USA

    R Graham Barr

  58. Department of Surgery and Pathology, University of Western Australia, Nedlands, Western Australia, Australia

    John Beilby

  59. PathWest Laboratory Medicine of Western Australia, Queen Elizabeth II Medical Centre, Nedlands, Western Australia, Australia

    John Beilby & Jennie Hui

  60. Faculty of Medicine, University of Split, Croatia, Split, Croatia.,

    Mladen Boban, Vesna Boraska, Ivana Kolcic, Ozren Polas̆ek & Tatijana Zemunik

  61. Department of Public Health and Community Medicine, Occupational and Environmental Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

    Jonas Brisman, Santosh Dahgam, Anna-Carin Olin & Fredrik Nyberg

  62. Division of Epidemiology and Public Health, School of Community Health Sciences and Nottingham Respiratory Biomedical Research Unit, University of Nottingham, Nottingham, UK

    John R Britton & Tricia McKeever

  63. Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium

    Guy G Brusselle

  64. MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK

    Cyrus Cooper, Karen A Jameson & Avan Aihie Sayer

  65. Chronic Disease Epidemiology, Swiss Tropical and Public Health (TPH) Institute, Basel, Switzerland

    Ivan Curjuric, Medea Imboden & Nicole Probst-Hensch

  66. University of Basel, Switzerland

    Ivan Curjuric, Medea Imboden & Nicole Probst-Hensch

  67. Department of Epidemiology and Population Health, Non-Communicable Diseases Epidemiology Unit, London School of Hygiene and Tropical Medicine, London, UK

    Shah Ebrahim

  68. South Asia Centre for Chronic Disease, New Delhi, India

    Shah Ebrahim

  69. Max Planck Institute for Psycholinguistics, Nijmegen, The Netherlands

    Clyde Francks

  70. MRC Unit for Lifelong Health and Ageing, London, UK

    Darya Gaysina, Rebecca Hardy, Andrew Wong & Diana Kuh

  71. School of Social and Community Medicine, University of Bristol, Bristol, UK

    Raquel Granell, John Henderson, Susan M Ring & Wendy L McArdle

  72. Hankinson Consulting, Inc, Athens, Georgia, USA

    John L Hankinson

  73. Medical Genetics Section, The University of Edinburgh, Edinburgh, UK

    Sarah E Harris

  74. Department of Epidemiology and Public Health, University College London, London, UK

    Aroon D Hingorani

  75. Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), The Netherlands

    Albert Hofman, Fernando Rivadeneira, André G Uitterlinden & Bruno H Ch Stricker

  76. Telethon Institute for Child Health Research and Centre for Child Health Research, The University of Western Australia, Perth, Western Australia, Australia

    Patrick G Holt & Peter D Sly

  77. School of Pathology and Laboratory Medicine, The University of Western Australia, Nedlands, Western Australia, Australia

    Jennie Hui

  78. School of Population Health, University of Western Australia, Nedlands, Western Australia, Australia

    Jennie Hui, Michael L Hunter & Arthur W Musk

  79. Molecular Medicine Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK

    Shona M Kerr & David J Porteous

  80. Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria

    Florian Kronenberg

  81. Department of Statistics, University of Oxford, Oxford, UK

    Jason Z Liu & Jonathan Marchini

  82. Medical Research Institute, The University of Dundee, Dundee, UK

    Andrew D Morris

  83. Department of Pulmonology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

    Dirkje S Postma

  84. Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands

    Fernando Rivadeneira, André G Uitterlinden & Bruno H Ch Stricker

  85. Division of Pulmonary Medicine, University Hospitals of Geneva, Geneva, Switzerland

    Thierry Rochat

  86. Department of Medicine, University of New Mexico, Albuquerque, New Mexico, USA

    Akshay Sood

  87. Geriatric Medicine Unit, The University of Edinburgh, Edinburgh, UK

    John M Starr

  88. Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

    Judith M Vonk & H Marike Boezen

  89. Department of Primary Care and Population Health, University College London, London, UK

    S Goya Wannamethee & Richard W Morris

  90. Division of Population Health Sciences and Education, St. George's University of London, London, UK

    Peter H Whincup, Alicja R Rudnicka & David P Strachan

  91. Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

    Cisca Wijmenga

  92. Division of Preventive Medicine, University of Alabama at Birmingham, Birmingham, USA

    O Dale Williams

  93. College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee, USA

    Bernd Meibohm

  94. Centre for Clinical Research, Haukeland University Hospital, Bergen, Norway

    Ernst Omenaas

  95. Department of Medicine, Division of Internal Medicine, Obesity Research Unit, Helsinki University Central Hospital, Helsinki, Finland

    Kirsi H Pietiläinen

  96. Department of Public Health, Hjelt Institute, University of Helsinki, Helsinki, Finland

    Kirsi H Pietiläinen & Jaakko Kaprio

  97. Institute for Molecular Medicine, University of Helsinki, Helsinki, Finland

    Kirsi H Pietiläinen, Samuli Ripatti, Ida Surakka & Jaakko Kaprio

  98. Pédiatrie, Centre Hospitalier Universitaire (CHU), Grenoble, France

    Isabelle Pin

  99. Inserm U823, Centre de Recherche Albert Bonniot, Grenoble, France

    Isabelle Pin

  100. Université Joseph Fourier, Grenoble, France

    Isabelle Pin

  101. Gen-Info Ltd, Zagreb, Croatia

    Ozren Polas̆ek & Igor Rudan

  102. Department of Children, Young People and Families, National Institute for Health and Welfare, Oulu, Finland

    Anneli Pouta & Marjo-Riitta Järvelin

  103. Institute of Clinical Medicine, University of Oulu, Oulu, Finland

    Anna-Liisa Hartikainen

  104. Department of Health Sciences, Gerontology Research Centre, University of Jyväskylä, Jyväskylä, Finland

    Taina Rantanen

  105. Department Of Chronic Disease Prevention, Public Health Genomics Unit, The National Institute for Health and Welfare, Helsinki, Finland

    Samuli Ripatti & Ida Surakka

  106. Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA

    Jerome I Rotter

  107. Institute of Epidemiology I, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany

    Holger Schulz, H-Erich Wichmann & Joachim Heinrich

  108. Institute for Community Medicine, Study of Health In Pomerania (SHIP)/Clinical Epidemiological Research, University of Greifswald, Greifswald, Germany

    Henry Völzke

  109. Institute of Medical Informatics, Biometry and Epidemiology, Chair of Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany

    H-Erich Wichmann

  110. Klinikum Grosshadern, Munich, Germany

    H-Erich Wichmann

  111. Division of Aging, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA

    Jemma B Wilk

  112. Institute of Lung Biology and Disease, Comprehensive Pneumology Center, Helmholtz Zentrum München, Neuherberg, Germany

    Matthias Wjst

  113. Institute for Medical Statistics and Epidemiology (IMSE), Technical University Munich, Munich, Germany

    Matthias Wjst

  114. Andrija Stampar School of Public Health, Faculty of Medicine, University of Zagreb, Zagreb, Croatia

    Lina Zgaga

  115. AstraZeneca Research and Development, Mölndal, Sweden

    Fredrik Nyberg

  116. Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK

    John W Holloway

  117. Infection, Inflammation and Immunity, Faculty of Medicine, University of Southampton, Southampton, UK

    John W Holloway

  118. Department of Clinical Physiology, University of Tampere and Tampere University Hospital, Tampere, Finland

    Mika Kähönen

  119. Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia

    Arthur W Musk

  120. MRC Health Protection Agency (HPA) Centre for Environment and Health, Imperial College London, London, UK

    Deborah L Jarvis, Marjo-Riitta Järvelin & Paul Elliott

  121. Department of Internal Medicine B, University Hospital Greifswald, Greifswald, Germany

    Sven Gläser

  122. Institute of Health Sciences, University of Oulu, Oulu, Finland

    Marjo-Riitta Järvelin

  123. Biocenter Oulu, University of Oulu, Oulu, Finland

    Marjo-Riitta Järvelin

  124. Department of Medical Informatics, Erasmus Medical Center, Rotterdam, The Netherlands

    Bruno H Ch Stricker

  125. Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts, USA

    George T O'Connor

  126. The National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, USA

    George T O'Connor

Authors
  1. María Soler Artigas
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Consortia

The International Lung Cancer Consortium

GIANT consortium

Contributions

Author contributions are listed in alphabetical order. See Supplementary Note for definitions of study acronyms.

Project conception, design and management. Stage 1 GWAS, AGES: G.E., M.G., V.G., T.B.H., L.J.L. ARIC: S.J.L., N.F., L.R.L., D.J.C., D.B.H., B.R.J., A.C.M., K.E.N. B58C-T1DGC: D.P.S. B58C -WTCCC: D.P.S. BHS1: A.L.J., A.W.M., L.J.P. CHS: S.A.G., S.R.H., T.L., B.M.P. CROATIA-Korcula: H.C., I.G., S.J., I.R., A.F.W., L.Z. CROATIA-Vis: H.C., C.H., O.P., I.R., A.F.W. ECRHS: D.L.J., E.O., I.P., M.W. EPIC: N.J.W. FHS: J.B.W., G.T.O. FTC: J.K., K.H.P., T. Rantanen. Health ABC: M.C.A., P.A.C., T.B.H., S.B.K., Y.L., B.M. Health 2000: M.H., M.K. KORA F4: J. Heinrich. KORA S3: C.G., H.-E.W. NFBC1966: P.E., A.-L.H., M.-R.J., A.P. ORCADES: H.C., S.H.W., J.F.W., A.F.W. RS: A. Hofman. SHIP: S.G., G.H., B.K., H.V. TwinsUK: T.D.S., G.Z. Stage 2 follow up, ADONIX: J. Brisman., A.-C.O. BHS2: J. Beilby. BRHS: R.W.M., S.G.W., P.H.W. BWHHS: G.D.S., S.E., D.A.L., P.H.W. CARDIA: A.S. CROATIA-Split: M.B., I.K., T.Z. GS: SFHS: C.M.J., S.M.K., A.D.M., D.J.P. HCS: C.C., J.W.H., A.A.S. LBC1936: I.J.D., S.E.H., J.M.S. LifeLines: H.M.B., D.S.P., J.M.V., C.W. MESA-Lung: R.G.B., J.L.H. Nottingham smokers: I.P.H. NSHD: R.H., D.K. SAPALDIA: N.P.-H., T. Rochat. Look-up studies, ALSPAC: R.G., J. Henderson. ILCCO: ILCCO data. Ox-GSK: C.F., J.M.

Phenotype collection and data management. Stage 1 GWAS, AGES: T.A. ARIC: D.J.C., N.F., L.R.L., A.C.M., K.E.N. B58C-T1DGC: A.R.R., D.P.S. B58C -WTCCC: A.R.R., D.P.S. BHS1: A.L.J., A.W.M., L.J.P. CHS: S.A.G., S.R.H., T.L., B.M.P. CROATIA-Korcula: I.G., S.J., O.P., I.R., L.Z. CROATIA-Vis: H.C., C.H., O.P., I.R., A.F.W. ECRHS: D.L.J., E.O., I.P., M.W. EPIC: N.J.W. FHS: J.B.W., G.T.O. FTC: J.K., K.H.P., T. Rantanen. Health ABC: P.A.C., B.M., W.T. Health 2000: M.H., M.K. KORA F4: S.K., H.S. KORA S3: N.P.-H. NFBC1966: P.E., A.-L.H., M.-R.J., A.P. ORCADES: H.C., S.H.W., J.F.W. RS: G.G.B., M.E., D.W.L., B.H.Ch.S. SHIP: S.G., B.K., H.V. TwinsUK: C.J.H., P.G. Hysi, M.M., T.D.S., G.Z. Stage 2 follow up, ADONIX: J. Brisman, A.-C.O. BHS2: J. Beilby, M.L.H. BRHS: R.W.M., S.G.W., P.H.W. BWHHS: G.D.S., S.E., D.A.L., P.H.W. CARDIA: O.D.W. CROATIA-Split: M.B., I.K., T.Z. GS: SFHS: C.M.J., A.D.M. HCS: C.C., K.A.J., A.A.S. LBC1936: I.J.D., L.M.L., J.M.S. LifeLines: D.S.P., J.M.V. MESA-Lung: R.G.B., J.L.H. Nottingham smokers: K.A.A.B., J.D.B., I.P.H., A. Henry, M.O., I. Sayers. NSHD: R.H., D.K. SAPALDIA: N.P.-H. Look-up studies, ALSPAC: R.G., J. Henderson. ILCCO: ILCCO. Raine: W.Q.A., P.G. Holt, C.E.P., P.D.S.

Genotyping. Stage 1 GWAS, B58C-T1DGC: W.L.M. B58C-WTCCC: W.L.M. BHS1: A.L.J., A.W.M., L.J.P. CHS: S.R.H., B.M.P., J.I.R. CROATIA-Vis: C.H., I.R., A.F.W. ECRHS: M.W. EPIC: I.B., R.J.F.L., J.H.Z. FTC: J.K. Health ABC: Y.L., K.L. Health 2000: S.R., I. Surakka. KORA F4: N.K. KORA S3: C.G. NFBC1966: P.E., A.-L.H., M.-R.J., A.P., A.R. ORCADES: H.C., J.F.W. RS: F.R., A.G.U. SHIP: G.H. TwinsUK: C.J.H., S.-Y.S. Stage 2 follow up, ADONIX: S.D., F.N., A.-C.O. BHS2: J. Beilby, G.C., J.H. BRHS: A.D.H., R.W.M. BWHHS: S.E., D.A.L. CARDIA: M.F., X.G. CROATIA-Split: V.B., T.Z. Gedling: J.R.B., T.M. GS: SFHS: C.M.J., S.M.K., D.J.P. HCS: J.W.H. LBC1936: I.J.D., S.E.H., L.M.L., J.M.S. LifeLines: C.W. MESA-Lung: S.S.R. NSHD: D.K., A.W. SAPALDIA: M.I., F.K. Look-up studies, ALSPAC: S.M.R., W.L.M. ILCCO: ILCCO. Raine: W.Q.A., C.E.P.

Data analysis. Stage 1 GWAS, AGES: G.K.G., A.V.S. ARIC: N.F., D.B.H., L.R.L. B58C–T1DGC: A.R.R., D.P.S. B58C -WTCCC: A.R.R., D.P.S. BHS1: N.M.W. CHS: K.D.M., J.I.R. CROATIA-Korcula: C.H., J.E.H., V.V. CROATIA-Vis: C.H., V.V. ECRHS: D.L.J., A.R. EPIC: J.H.Z. FHS: J.B.W. FTC: I. Surakka. Health ABC: P.A.C., Y.L., K.L., W.T. Health 2000: M.K., S.R., I. Surakka. KORA S3: E.A. NFBC1966: A.R. ORCADES: C.H., V.V. RS: M.E., D.W.L. SHIP: S.G., G.H., B.K., H.V. TwinsUK: M.M., G.Z. Stage 2 follow-up studies, ADONIX: S.D., F.N. BHS2: G.C. BRHS: R.W.M. BWHHS: D.A.L. CARDIA: M.F., X.G. HCS: J.W.H., K.A.J. LBC1936: L.M.L. LifeLines: H.M.B. MESA-Lung: A.M., S.S.R. Nottingham smokers: I. Sayers, A. Henry. NSHD: D.G., R.H. SAPALDIA: I.C., M.I. Look-up studies, ALSPAC: D.M.E. ILCCO: ILCCO. Ox-GSK: J.Z.L. Raine: W.Q.A.

Analysis group: SpiroMeta consortium: I.P.H., T.J., M.S.A., M.D.T., L.V.W. CHARGE consortium: N.F., S.J.L., D.W.L., K.D.M., A.V.S., W.T., J.B.W.

Expression profiling and bioinformatics group: SpiroMeta consortium: I.P.H., M.O., I. Sayers, M.S.A., M.D.T., L.V.W. CHARGE consortium: S.A.G., D.W.L.

Writing group: SpiroMeta consortium: P.E., I.P.H., M.O., M.S.A., D.P.S., M.D.T., L.V.W. CHARGE consortium: S.J.L., D.W.L., S.A.G., G.T.O., V.G., B.H.Ch.S., W.T.

Corresponding authors

Correspondence to Stephanie J London or Martin D Tobin.

Ethics declarations

Competing interests

I.B. and spouse own stock in Incyte Ltd and GlaxoSmithKline. F.N. is employed by AstraZeneca R&D, 431 83 Mölndal, Sweden. D.S.P. has received unrestricted research grants from and has been a consultant to AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Nycomed and TEVA. C.F. is a full-time employee of GlaxoSmithKline (GSK), and GSK also funded several aspects of the study as detailed in the Acknowledgements section for Ox-GSK.

Additional information

A full list of members is provided in the Supplementary Note.

A full list of members is provided in the Supplementary Note.

Supplementary information

Supplementary Text and Figures

Supplementary Figure 1, Supplementary Tables 1–6 and Supplementary Note (PDF 3692 kb)

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Artigas, M., Loth, D., Wain, L. et al. Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function. Nat Genet 43, 1082–1090 (2011). https://doi.org/10.1038/ng.941

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