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Nat Genet. 2017 Mar;49(3):426-432. doi: 10.1038/ng.3752. Epub 2017 Feb 6.

Genetic loci associated with chronic obstructive pulmonary disease overlap with loci for lung function and pulmonary fibrosis.

Author information

1
Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
2
Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
3
University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, the Netherlands.
4
University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, the Netherlands.
5
Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, Québec, Canada.
6
Department of Molecular Medicine, Laval University, Québec, Québec, Canada.
7
Genetic Epidemiology Group, Department of Health Sciences, University of Leicester, Leicester, UK.
8
Division of Respiratory Medicine, Queen's Medical Centre, University of Nottingham, Nottingham, UK.
9
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.
10
Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USA.
11
Population Health Research Institute, St George's, University of London, London, UK.
12
Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.
13
Department of Epidemiology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
14
Department of Medicine, Division of Pulmonary and Critical Care Medicine, National Jewish Health, Denver, Colorado, USA.
15
Division of General Internal Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
16
Cardiovascular Health Research Unit, University of Washington, Seattle, Washington, USA.
17
Department of Medicine, University of Washington, Seattle, Washington, USA.
18
Department of Biostatistics, University of Washington, Seattle, Washington, USA.
19
Department of Epidemiology, University of Washington, Seattle, Washington, USA.
20
Group Health Research Institute, Group Health Cooperative, Seattle, Washington, USA.
21
Department of Health Services, University of Washington, Seattle, Washington, USA.
22
Computational Medicine Core, Center for Lung Biology, UW Medicine Sleep Center, Department of Medicine, University of Washington, Seattle, Washington, USA.
23
Department of Pulmonology, University Medical Center Utrecht, University of Utrecht, Utrecht, the Netherlands.
24
University of Groningen, University Medical Center Groningen, Center for Medical Imaging, Groningen, the Netherlands.
25
University of Groningen, University Medical Center Groningen, Department of Pulmonology, Groningen, the Netherlands.
26
GSK R&D, King of Prussia, Pennsylvania, USA.
27
Pulmonary, Critical Care, Sleep and Allergy Division, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA.
28
Clinical Discovery Unit, AstraZeneca, Cambridge, UK.
29
School of Biological Sciences, University of Manchester, Manchester, UK.
30
Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, GRIAC Research Institute, Groningen, the Netherlands.
31
University of British Columbia Center for Heart Lung Innovation and Institute for Heart and Lung Health, St Paul's Hospital, Vancouver, British Columbia, Canada.
32
Department of Neurology, Boston University School of Medicine, Boston, Massachusetts, USA.
33
Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA.
34
National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, USA.
35
Pulmonary Center, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.
36
Department of Internal Medicine and Environmental Health Center, School of Medicine, Kangwon National University, Chuncheon, Republic of Korea.
37
Department of Pulmonary and Critical Care Medicine, and Clinical Research Center for Chronic Obstructive Airway Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
38
Department of Public Health, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands.
39
Lovelace Respiratory Research Institute, Albuquerque, New Mexico, USA.
40
Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, USA.
41
Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia, USA.
42
Department of Medicine, College of Physicians and Surgeons and Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, USA.
43
VA Boston Healthcare System and Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.
44
Department of Clinical Science, University of Bergen, Bergen, Norway.
45
Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
46
Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
47
Department of Respiratory Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.
48
Netherlands Health Care Inspectorate, The Hague, the Netherlands.
49
Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.
50
Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), Leiden, the Netherlands.
51
Center for Genomics and Personalized Medicine Research, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
52
Cardiovascular Research Institute and Department of Medicine, Division of Pulmonary, Critical Care, Sleep, and Allergy, University of California at San Francisco, San Francisco, California, USA.
53
University College London, London, UK.
54
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
55
Seoul National University College of Medicine, SMG-SNU Boramae Medical Center, Seoul, Republic of Korea.
56
2nd Department of Respiratory Medicine, Institute of Tuberculosis and Lung Diseases, Warsaw, Poland.
57
Center for Genes, Environment and Health, National Jewish Health, Denver, Colorado, USA.
58
Department of Biostatistics and Informatics, University of Colorado Denver, Aurora, Colorado, USA.
59
Department of Medicine, School of Medicine, University of Colorado Denver, Aurora, Colorado, USA.
60
Department of Immunology, School of Medicine, University of Colorado Denver, Aurora, Colorado, USA.
61
University of Edinburgh, Edinburgh, UK.
62
National Institute for Health Research (NIHR) Leicester Respiratory Biomedical Research Unit, Glenfield Hospital, Leicester, UK.

Abstract

Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality worldwide. We performed a genetic association study in 15,256 cases and 47,936 controls, with replication of select top results (P < 5 × 10-6) in 9,498 cases and 9,748 controls. In the combined meta-analysis, we identified 22 loci associated at genome-wide significance, including 13 new associations with COPD. Nine of these 13 loci have been associated with lung function in general population samples, while 4 (EEFSEC, DSP, MTCL1, and SFTPD) are new. We noted two loci shared with pulmonary fibrosis (FAM13A and DSP) but that had opposite risk alleles for COPD. None of our loci overlapped with genome-wide associations for asthma, although one locus has been implicated in joint susceptibility to asthma and obesity. We also identified genetic correlation between COPD and asthma. Our findings highlight new loci associated with COPD, demonstrate the importance of specific loci associated with lung function to COPD, and identify potential regions of genetic overlap between COPD and other respiratory diseases.

PMID:
28166215
PMCID:
PMC5381275
DOI:
10.1038/ng.3752
[Indexed for MEDLINE]
Free PMC Article

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