Abstract

We performed a genome-wide association study for chronic obstructive pulmonary disease (COPD) in three population cohorts, including 2,940 cases and 1,380 controls who were current or former smokers with normal lung function. We identified a new susceptibility locus at 4q22.1 in FAM13A and replicated this association in one case-control group (n = 1,006) and two family-based cohorts (n = 3,808) (rs7671167, combined P = 1.2 × 10−11, combined odds ratio in case-control studies 0.76, 95% confidence interval 0.69–0.83).

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Acknowledgements

This work was supported by US National Institutes of Health (NIH) grants R01 HL075478, R01 HL084323, P01 HL083069, U01 HL089856 (E.K.S.), K12HL089990 (M.H.C) and U01 HL089897 (J.D.C.). The National Emphysema Treatment Trial was supported by the National Heart, Lung, and Blood Institute, the Centers for Medicare and Medicaid Services and the Agency for Healthcare Research and Quality. The Normative Aging Study is supported by the Cooperative Studies Program/ERIC of the US Department of Veterans Affairs and is a component of the Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC). The Norway cohort, the ECLIPSE study (Clinicaltrials.gov identifier NCT00292552; GSK Code SCO104960) and the ICGN study are funded by GlaxoSmithKline. Further acknowledgments are given in the Supplementary Note.

Author information

Author notes

    • Sreekumar G Pillai

    Current address: Hoffman La Roche, Nutley, New Jersey, USA.

Affiliations

  1. Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.

    • Michael H Cho
    • , Nadia Boutaoui
    • , Barbara J Klanderman
    • , Jody S Sylvia
    • , John P Ziniti
    • , Craig P Hersh
    • , Dawn L DeMeo
    • , Gary M Hunninghake
    • , Augusto A Litonjua
    •  & Edwin K Silverman
  2. Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.

    • Michael H Cho
    • , Craig P Hersh
    • , Dawn L DeMeo
    • , Gary M Hunninghake
    • , Augusto A Litonjua
    •  & Edwin K Silverman
  3. Veterans Administration Boston Healthcare System, Boston, Massachusetts, USA.

    • David Sparrow
  4. School of Public Health, Boston University, Boston, Massachusetts, USA.

    • David Sparrow
  5. School of Medicine, Boston University, Boston, Massachusetts, USA.

    • David Sparrow
  6. Harvard School of Public Health, Harvard University, Boston, Massachusetts, USA.

    • Christoph Lange
    •  & Sungho Won
  7. National Jewish Medical and Research Center, Denver, Colorado, USA.

    • James R Murphy
    • , Elizabeth A Regan
    • , Barry J Make
    •  & James D Crapo
  8. Johns Hopkins School of Public Health, Baltimore, Maryland, USA.

    • Terri H Beaty
  9. Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Aurora, Colorado, USA.

    • John E Hokanson
  10. GlaxoSmithKline Research and Development, King of Prussia, Pennsylvania.

    • Xiangyang Kong
    •  & Ruth Tal-Singer
  11. GlaxoSmithKline Research and Development, Research Triangle Park, North Carolina, USA.

    • Wayne H Anderson
    •  & Sreekumar G Pillai
  12. Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.

    • David A Lomas
  13. Haukeland University Hospital and Institute of Medicine, University of Bergen, Bergen, Norway.

    • Per Bakke
    •  & Amund Gulsvik

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Contributions

Study design: E.K.S., M.H.C., A.A.L., D.S., S.G.P., X.K., W.H.A., R.T.-S., D.A.L., P.B., A.G., J.R.M., T.H.B., E.A.R., B.J.M., J.E.H., J.D.C., C.P.H. and D.L.D. Sample collection and phenotyping: A.A.L., D.S., S.G.P., X.K., W.H.A., R.T.-S., D.A.L., P.B., A.G., E.A.R., B.J.M., J.D.C., E.K.S. Genotyping: N.B., B.J.K., M.H.C., S.G.P., X.K. Informatics: M.H.C., J.S.S., J.P.Z., B.J.K., N.B. Statistical analysis: M.H.C., C.L., S.W., E.K.S. Manuscript writing: M.H.C., G.M.H., E.K.S. All authors reviewed and approved the manuscript.

Competing interests

E.K.S. has received grant support and consulting and speaker's fees from GlaxoSmithKline, consulting and speaker's fees from Astra-Zeneca and speaker's fees from Bayer and Wyeth. D.A.L. has received grant support, lecture fees and consultancy fees from GlaxoSmithKline. S.G.P, X.Q.K., W.H.A. and R.M.T. are employees of GlaxoSmithKline.

Corresponding author

Correspondence to Edwin K Silverman.

Supplementary information

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    Supplementary Text and Figures

    Supplementary Methods, Supplementary Note, Supplementary Figures 1–3 and Supplementary Tables 1–4

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DOI

https://doi.org/10.1038/ng.535

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