Article | Published:

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

Nature Genetics volume 43, pages 10821090 (2011) | Download Citation

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.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    et al. Evidence for major genes influencing pulmonary function in the NHLBI family heart study. Genet. Epidemiol. 19, 81–94 (2000).

  2. 2.

    et al. Impaired lung function and mortality risk in men and women: findings from the Renfrew and Paisley prospective population study. Br. Med. J. 313, 711–715, discussion 715–716 (1996).

  3. 3.

    Ventilatory function, height, and mortality among lifelong non-smokers. J. Epidemiol. Community Health 46, 66–70 (1992).

  4. 4.

    , & Forced expiratory volume in one second: not just a lung function test but a marker of premature death from all causes. Eur. Respir. J. 30, 616–622 (2007).

  5. 5.

    et al. Chronic obstructive pulmonary disease: current burden and future projections. Eur. Respir. J. 27, 397–412 (2006).

  6. 6.

    & Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med. 3, e442 (2006).

  7. 7.

    et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am. J. Respir. Crit. Care Med. 176, 532–555 (2007).

  8. 8.

    et al. Meta-analyses of genome-wide association studies identify multiple loci associated with pulmonary function. Nat. Genet. 42, 45–52 (2010).

  9. 9.

    et al. Genome-wide association study identifies five loci associated with lung function. Nat. Genet. 42, 36–44 (2010).

  10. 10.

    et al. A genome-wide association study in chronic obstructive pulmonary disease (COPD): identification of two major susceptibility loci. PLoS Genet. 5, e1000421 (2009).

  11. 11.

    et al. A genome-wide association study of pulmonary function measures in the Framingham Heart Study. PLoS Genet. 5, e1000429 (2009).

  12. 12.

    et al. Genomic inflation factors under polygenic inheritance. Eur. J. Hum. Genet. 19, 807–812 (2011).

  13. 13.

    et al. Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies. Nat. Genet. 42, 1077–1085 (2010).

  14. 14.

    et al. Hundreds of variants clustered in genomic loci and biological pathways affect human height. Nature 467, 832–838 (2010).

  15. 15.

    et al. Genome-wide association scan meta-analysis identifies three loci influencing adiposity and fat distribution. PLoS Genet. 5, e1000508 (2009).

  16. 16.

    et al. A genome-wide association study of global gene expression. Nat. Genet. 39, 1202–1207 (2007).

  17. 17.

    , , & The major antigen of elastin-associated microfibrils is a 31-kDa glycoprotein. J. Biol. Chem. 261, 11429–11436 (1986).

  18. 18.

    et al. Rootletin, a novel coiled-coil protein, is a structural component of the ciliary rootlet. J. Cell Biol. 159, 431–440 (2002).

  19. 19.

    et al. Retinoic acid receptor-β: an endogenous inhibitor of the perinatal formation of pulmonary alveoli. Physiol. Genomics 4, 51–57 (2000).

  20. 20.

    , , & Cdc123 and checkpoint forkhead associated with RING proteins control the cell cycle by controlling eIF2γ abundance. J. Biol. Chem. 279, 44656–44666 (2004).

  21. 21.

    et al. Decreased histone deacetylase activity in chronic obstructive pulmonary disease. N. Engl. J. Med. 352, 1967–1976 (2005).

  22. 22.

    et al. Parental smoking modifies the relation between genetic variation in tumor necrosis factor-α (TNF) and childhood asthma. Environ. Health Perspect. 115, 616–622 (2007).

  23. 23.

    et al. Tumour necrosis factor gene complex polymorphisms in chronic obstructive pulmonary disease. Respir. Med. 101, 340–344 (2007).

  24. 24.

    et al. Transforming growth factor-β2 induces bronchial epithelial mucin expression in asthma. Am. J. Pathol. 165, 1097–1106 (2004).

  25. 25.

    et al. Meta-analysis and imputation refines the association of 15q25 with smoking quantity. Nat. Genet. 42, 436–440 (2010).

  26. 26.

    et al. A genome-wide association study of lung cancer identifies a region of chromosome 5p15 associated with risk for adenocarcinoma. Am. J. Hum. Genet. 85, 679–691 (2009).

  27. 27.

    et al. Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants. Nat. Genet. 41, 334–341 (2009).

  28. 28.

    et al. Identification of candidate loci at 6p21 and 21q22 in a genome-wide association study of cardiac manifestations of neonatal lupus. Arthritis Rheum. 62, 3415–3424 (2010).

  29. 29.

    et al. Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci. Nat. Genet. 40, 204–210 (2008).

  30. 30.

    et al. Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes. Nat. Genet. 40, 638–645 (2008).

  31. 31.

    et al. Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. Nat. Genet. 41, 703–707 (2009).

  32. 32.

    et al. Genome-wide association study of blood pressure and hypertension. Nat. Genet. 41, 677–687 (2009).

  33. 33.

    et al. Genome-wide association study identifies eight loci associated with blood pressure. Nat. Genet. 41, 666–676 (2009).

  34. 34.

    et al. Estimation of effect size distribution from genome-wide association studies and implications for future discoveries. Nat. Genet. 42, 570–575 (2010).

  35. 35.

    et al. Genome partitioning of genetic variation for complex traits using common SNPs. Nat. Genet. 43, 519–525 (2011).

  36. 36.

    et al. The natural history of chronic airflow obstruction revisited: an analysis of the framingham offspring cohort. Am. J. Respir. Crit. Care Med. 180, 3–10 (2009).

  37. 37.

    , & Spirometric reference values from a sample of the general U.S. population. Am. J. Respir. Crit. Care Med. 159, 179–187 (1999).

  38. 38.

    et al. Utility of genetic and non-genetic risk factors in prediction of type 2 diabetes: Whitehall II prospective cohort study. Br. Med. J. 340, b4838 (2010).

  39. 39.

    et al. Performance of common genetic variants in breast-cancer risk models. N. Engl. J. Med. 362, 986–993 (2010).

  40. 40.

    , , , & Epithelial-derived TGF-β2 modulates basal and wound-healing subepithelial matrix homeostasis. Am. J. Physiol. Lung Cell. Mol. Physiol. 291, L1277–L1285 (2006).

  41. 41.

    , , & The story of SPATA2 (spermatogenesis-associated protein 2): from Sertoli cells to pancreatic β-cells. Curr. Genomics 10, 361–363 (2009).

  42. 42.

    , , & Armadillo-repeat protein functions: questions for little creatures. Trends Cell Biol. 20, 470–481 (2010).

  43. 43.

    et al. Identification and molecular characterization of NKp30, a novel triggering receptor involved in natural cytotoxicity mediated by human natural killer cells. J. Exp. Med. 190, 1505–1516 (1999).

  44. 44.

    , & Beyond endocytosis: LRP function in cell migration, proliferation and vascular permeability. J. Thromb. haemost. 3, 1884–1893 (2005).

  45. 45.

    , & Coiled coils: a highly versatile protein folding motif. Trends Cell Biol. 11, 82–88 (2001).

  46. 46.

    & Characterization of basolateral K+ channels underlying anion secretion in the human airway cell line Calu-3. J. Physiol. (Lond.) 538, 747–757 (2002).

  47. 47.

    & Mach 1.0: rapid haplotype construction and missing genotype inference. Am. J. Hum. Genet. S79, 2290 (2006).

  48. 48.

    , , , & A new multipoint method for genome-wide association studies by imputation of genotypes. Nat. Genet. 39, 906–913 (2007).

  49. 49.

    & Imputation-based analysis of association studies: candidate regions and quantitative traits. PLoS Genet. 3, e114 (2007).

  50. 50.

    & Genomic control for association studies. Biometrics 55, 997–1004 (1999).

  51. 51.

    et al. Variants in FAM13A are associated with chronic obstructive pulmonary disease. Nat. Genet. 42, 200–202 (2010).

  52. 52.

    et al. Loci identified by genome-wide association studies influence different disease-related phenotypes in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 182, 1498–1505 (2010).

  53. 53.

    , , , & Common inherited variation in mitochondrial genes is not enriched for associations with type 2 diabetes or related glycemic traits. PLoS Genet. 6, e1001058 (2010).

  54. 54.

    et al. Identifying relationships among genomic disease regions: predicting genes at pathogenic SNP associations and rare deletions. PLoS Genet. 5, e1000534 (2009).

Download references

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

    • 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
    •  & Martin D Tobin

    These authors contributed equally to this work.

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. Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, 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. Interfaculty Institute for Genetics and Functional Genomics, Department of 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. Busselton Population Medical Research Foundation, Department of Respiratory Medicine, 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. Occupational and Environmental Medicine, Department of Public Health and Community 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. Non-Communicable Diseases Epidemiology Unit, Department of Epidemiology and Population Health, 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. Obesity Research Unit, Department of Medicine, Division of Internal Medicine, Helsinki University Central Hospital, Helsinki, Finland.

    • Kirsi H Pietiläinen
  96. Hjelt Institute, Department of Public Health, 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. Gerontology Research Centre, Department of Health Sciences, University of Jyväskylä, Jyväskylä, Finland.

    • Taina Rantanen
  105. Public Health Genomics Unit, Department Of Chronic Disease Prevention, 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. University Hospital Greifswald, Department of Internal Medicine B, 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

Consortia

  1. The International Lung Cancer Consortium

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

  2. GIANT consortium

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

Authors

  1. Search for María Soler Artigas in:

  2. Search for Daan W Loth in:

  3. Search for Louise V Wain in:

  4. Search for Sina A Gharib in:

  5. Search for Ma'en Obeidat in:

  6. Search for Wenbo Tang in:

  7. Search for Guangju Zhai in:

  8. Search for Jing Hua Zhao in:

  9. Search for Albert Vernon Smith in:

  10. Search for Jennifer E Huffman in:

  11. Search for Eva Albrecht in:

  12. Search for Catherine M Jackson in:

  13. Search for David M Evans in:

  14. Search for Gemma Cadby in:

  15. Search for Myriam Fornage in:

  16. Search for Ani Manichaikul in:

  17. Search for Lorna M Lopez in:

  18. Search for Toby Johnson in:

  19. Search for Melinda C Aldrich in:

  20. Search for Thor Aspelund in:

  21. Search for Inês Barroso in:

  22. Search for Harry Campbell in:

  23. Search for Patricia A Cassano in:

  24. Search for David J Couper in:

  25. Search for Gudny Eiriksdottir in:

  26. Search for Nora Franceschini in:

  27. Search for Melissa Garcia in:

  28. Search for Christian Gieger in:

  29. Search for Gauti Kjartan Gislason in:

  30. Search for Ivica Grkovic in:

  31. Search for Christopher J Hammond in:

  32. Search for Dana B Hancock in:

  33. Search for Tamara B Harris in:

  34. Search for Adaikalavan Ramasamy in:

  35. Search for Susan R Heckbert in:

  36. Search for Markku Heliövaara in:

  37. Search for Georg Homuth in:

  38. Search for Pirro G Hysi in:

  39. Search for Alan L James in:

  40. Search for Stipan Jankovic in:

  41. Search for Bonnie R Joubert in:

  42. Search for Stefan Karrasch in:

  43. Search for Norman Klopp in:

  44. Search for Beate Koch in:

  45. Search for Stephen B Kritchevsky in:

  46. Search for Lenore J Launer in:

  47. Search for Yongmei Liu in:

  48. Search for Laura R Loehr in:

  49. Search for Kurt Lohman in:

  50. Search for Ruth J F Loos in:

  51. Search for Thomas Lumley in:

  52. Search for Khalid A Al Balushi in:

  53. Search for Wei Q Ang in:

  54. Search for R Graham Barr in:

  55. Search for John Beilby in:

  56. Search for John D Blakey in:

  57. Search for Mladen Boban in:

  58. Search for Vesna Boraska in:

  59. Search for Jonas Brisman in:

  60. Search for John R Britton in:

  61. Search for Guy G Brusselle in:

  62. Search for Cyrus Cooper in:

  63. Search for Ivan Curjuric in:

  64. Search for Santosh Dahgam in:

  65. Search for Ian J Deary in:

  66. Search for Shah Ebrahim in:

  67. Search for Mark Eijgelsheim in:

  68. Search for Clyde Francks in:

  69. Search for Darya Gaysina in:

  70. Search for Raquel Granell in:

  71. Search for Xiangjun Gu in:

  72. Search for John L Hankinson in:

  73. Search for Rebecca Hardy in:

  74. Search for Sarah E Harris in:

  75. Search for John Henderson in:

  76. Search for Amanda Henry in:

  77. Search for Aroon D Hingorani in:

  78. Search for Albert Hofman in:

  79. Search for Patrick G Holt in:

  80. Search for Jennie Hui in:

  81. Search for Michael L Hunter in:

  82. Search for Medea Imboden in:

  83. Search for Karen A Jameson in:

  84. Search for Shona M Kerr in:

  85. Search for Ivana Kolcic in:

  86. Search for Florian Kronenberg in:

  87. Search for Jason Z Liu in:

  88. Search for Jonathan Marchini in:

  89. Search for Tricia McKeever in:

  90. Search for Andrew D Morris in:

  91. Search for Anna-Carin Olin in:

  92. Search for David J Porteous in:

  93. Search for Dirkje S Postma in:

  94. Search for Stephen S Rich in:

  95. Search for Susan M Ring in:

  96. Search for Fernando Rivadeneira in:

  97. Search for Thierry Rochat in:

  98. Search for Avan Aihie Sayer in:

  99. Search for Ian Sayers in:

  100. Search for Peter D Sly in:

  101. Search for George Davey Smith in:

  102. Search for Akshay Sood in:

  103. Search for John M Starr in:

  104. Search for André G Uitterlinden in:

  105. Search for Judith M Vonk in:

  106. Search for S Goya Wannamethee in:

  107. Search for Peter H Whincup in:

  108. Search for Cisca Wijmenga in:

  109. Search for O Dale Williams in:

  110. Search for Andrew Wong in:

  111. Search for Massimo Mangino in:

  112. Search for Kristin D Marciante in:

  113. Search for Wendy L McArdle in:

  114. Search for Bernd Meibohm in:

  115. Search for Alanna C Morrison in:

  116. Search for Kari E North in:

  117. Search for Ernst Omenaas in:

  118. Search for Lyle J Palmer in:

  119. Search for Kirsi H Pietiläinen in:

  120. Search for Isabelle Pin in:

  121. Search for Ozren Polas̆ek in:

  122. Search for Anneli Pouta in:

  123. Search for Bruce M Psaty in:

  124. Search for Anna-Liisa Hartikainen in:

  125. Search for Taina Rantanen in:

  126. Search for Samuli Ripatti in:

  127. Search for Jerome I Rotter in:

  128. Search for Igor Rudan in:

  129. Search for Alicja R Rudnicka in:

  130. Search for Holger Schulz in:

  131. Search for So-Youn Shin in:

  132. Search for Tim D Spector in:

  133. Search for Ida Surakka in:

  134. Search for Veronique Vitart in:

  135. Search for Henry Völzke in:

  136. Search for Nicholas J Wareham in:

  137. Search for Nicole M Warrington in:

  138. Search for H-Erich Wichmann in:

  139. Search for Sarah H Wild in:

  140. Search for Jemma B Wilk in:

  141. Search for Matthias Wjst in:

  142. Search for Alan F Wright in:

  143. Search for Lina Zgaga in:

  144. Search for Tatijana Zemunik in:

  145. Search for Craig E Pennell in:

  146. Search for Fredrik Nyberg in:

  147. Search for Diana Kuh in:

  148. Search for John W Holloway in:

  149. Search for H Marike Boezen in:

  150. Search for Debbie A Lawlor in:

  151. Search for Richard W Morris in:

  152. Search for Nicole Probst-Hensch in:

  153. Search for Jaakko Kaprio in:

  154. Search for James F Wilson in:

  155. Search for Caroline Hayward in:

  156. Search for Mika Kähönen in:

  157. Search for Joachim Heinrich in:

  158. Search for Arthur W Musk in:

  159. Search for Deborah L Jarvis in:

  160. Search for Sven Gläser in:

  161. Search for Marjo-Riitta Järvelin in:

  162. Search for Bruno H Ch Stricker in:

  163. Search for Paul Elliott in:

  164. Search for George T O'Connor in:

  165. Search for David P Strachan in:

  166. Search for Stephanie J London in:

  167. Search for Ian P Hall in:

  168. Search for Vilmundur Gudnason in:

  169. Search for Martin D Tobin in:

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.

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.

Corresponding authors

Correspondence to Stephanie J London or Martin D Tobin.

Supplementary information

PDF files

  1. 1.

    Supplementary Text and Figures

    Supplementary Figure 1, Supplementary Tables 1–6 and Supplementary Note

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/ng.941

Further reading