Journal article
Genetic loci associated with chronic obstructive pulmonary disease overlap with loci for lung function and pulmonary fibrosis
Nature genetics, Vol.49(3), pp.426-432
03/2017
DOI: 10.1038/ng.3752
PMCID: PMC5381275
PMID: 28166215
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
) 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.
Details
- Title: Subtitle
- Genetic loci associated with chronic obstructive pulmonary disease overlap with loci for lung function and pulmonary fibrosis
- Creators
- Brian D Hobbs - Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USAKim de Jong - University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, the NetherlandsMaxime Lamontagne - Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, Québec, CanadaYohan Bossé - Department of Molecular Medicine, Laval University, Québec, Québec, CanadaNick Shrine - Genetic Epidemiology Group, Department of Health Sciences, University of Leicester, Leicester, UKMaría Soler Artigas - Genetic Epidemiology Group, Department of Health Sciences, University of Leicester, Leicester, UKLouise V Wain - Genetic Epidemiology Group, Department of Health Sciences, University of Leicester, Leicester, UKIan P Hall - Division of Respiratory Medicine, Queen's Medical Centre, University of Nottingham, Nottingham, UKVictoria E Jackson - Genetic Epidemiology Group, Department of Health Sciences, University of Leicester, Leicester, UKAnnah B Wyss - 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, USAStephanie J London - 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, USAKari E North - Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USANora Franceschini - Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USADavid P Strachan - Population Health Research Institute, St George's, University of London, London, UKTerri H Beaty - Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USAJohn E Hokanson - Department of Epidemiology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USAJames D Crapo - Department of Medicine, Division of Pulmonary and Critical Care Medicine, National Jewish Health, Denver, Colorado, USAPeter J Castaldi - Division of General Internal Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USARobert P Chase - Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USATraci M Bartz - Department of Biostatistics, University of Washington, Seattle, Washington, USASusan R Heckbert - Group Health Research Institute, Group Health Cooperative, Seattle, Washington, USABruce M Psaty - Department of Health Services, University of Washington, Seattle, Washington, USASina A Gharib - Computational Medicine Core, Center for Lung Biology, UW Medicine Sleep Center, Department of Medicine, University of Washington, Seattle, Washington, USAPieter Zanen - Department of Pulmonology, University Medical Center Utrecht, University of Utrecht, Utrecht, the NetherlandsJan W Lammers - Department of Pulmonology, University Medical Center Utrecht, University of Utrecht, Utrecht, the NetherlandsMatthijs Oudkerk - University of Groningen, University Medical Center Groningen, Center for Medical Imaging, Groningen, the NetherlandsH J Groen - University of Groningen, University Medical Center Groningen, Department of Pulmonology, Groningen, the NetherlandsNicholas Locantore - GSK R&D, King of Prussia, Pennsylvania, USARuth Tal-Singer - GSK R&D, King of Prussia, Pennsylvania, USAStephen I Rennard - Clinical Discovery Unit, AstraZeneca, Cambridge, UKJørgen Vestbo - School of Biological Sciences, University of Manchester, Manchester, UKWim Timens - Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, GRIAC Research Institute, Groningen, the NetherlandsPeter D Paré - University of British Columbia Center for Heart Lung Innovation and Institute for Heart and Lung Health, St Paul's Hospital, Vancouver, British Columbia, CanadaJeanne C Latourelle - Department of Neurology, Boston University School of Medicine, Boston, Massachusetts, USAJosée Dupuis - National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, USAGeorge T O'Connor - Pulmonary Center, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USAJemma B Wilk - National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, USAWoo Jin Kim - Department of Internal Medicine and Environmental Health Center, School of Medicine, Kangwon National University, Chuncheon, Republic of KoreaMi Kyeong Lee - Department of Internal Medicine and Environmental Health Center, School of Medicine, Kangwon National University, Chuncheon, Republic of KoreaYeon-Mok Oh - 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 KoreaJudith M Vonk - University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, the NetherlandsHarry J de Koning - Department of Public Health, Erasmus Medical Center Rotterdam, Rotterdam, the NetherlandsShuguang Leng - Lovelace Respiratory Research Institute, Albuquerque, New Mexico, USASteven A Belinsky - Lovelace Respiratory Research Institute, Albuquerque, New Mexico, USAYohannes Tesfaigzi - Lovelace Respiratory Research Institute, Albuquerque, New Mexico, USAAni Manichaikul - Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia, USAXin-Qun Wang - Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia, USAStephen S Rich - Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia, USAR Graham Barr - Department of Medicine, College of Physicians and Surgeons and Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, USADavid Sparrow - VA Boston Healthcare System and Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USAAugusto A Litonjua - Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USAPer Bakke - Department of Clinical Science, University of Bergen, Bergen, NorwayAmund Gulsvik - Department of Clinical Science, University of Bergen, Bergen, NorwayLies Lahousse - Department of Respiratory Medicine, Ghent University Hospital, Ghent, BelgiumGuy G Brusselle - Department of Respiratory Medicine, Erasmus Medical Center, Rotterdam, the NetherlandsBruno H Stricker - Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), Leiden, the NetherlandsAndré G Uitterlinden - Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), Leiden, the NetherlandsElizabeth J Ampleford - Center for Genomics and Personalized Medicine Research, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USAEugene R Bleecker - Center for Genomics and Personalized Medicine Research, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USAPrescott G Woodruff - Cardiovascular Research Institute and Department of Medicine, Division of Pulmonary, Critical Care, Sleep, and Allergy, University of California at San Francisco, San Francisco, California, USADeborah A Meyers - Center for Genomics and Personalized Medicine Research, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USADandi Qiao - Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USADavid A Lomas - University College London, London, UKJae-Joon Yim - Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of KoreaDeog Kyeom Kim - Seoul National University College of Medicine, SMG-SNU Boramae Medical Center, Seoul, Republic of KoreaIwona Hawrylkiewicz - 2nd Department of Respiratory Medicine, Institute of Tuberculosis and Lung Diseases, Warsaw, PolandPawel Sliwinski - 2nd Department of Respiratory Medicine, Institute of Tuberculosis and Lung Diseases, Warsaw, PolandMegan Hardin - Clinical Discovery Unit, AstraZeneca, Cambridge, UKTasha E Fingerlin - Department of Biostatistics and Informatics, University of Colorado Denver, Aurora, Colorado, USADavid A Schwartz - Department of Immunology, School of Medicine, University of Colorado Denver, Aurora, Colorado, USADirkje S Postma - University of Groningen, University Medical Center Groningen, Department of Pulmonology, Groningen, the NetherlandsWilliam MacNee - University of Edinburgh, Edinburgh, UKMartin D Tobin - National Institute for Health Research (NIHR) Leicester Respiratory Biomedical Research Unit, Glenfield Hospital, Leicester, UKEdwin K Silverman - Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USAH Marike Boezen - University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, the NetherlandsMichael H Cho - Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USACOPDGene InvestigatorsECLIPSE InvestigatorsLifeLines InvestigatorsSPIROMICS Research GroupInternational COPD Genetics Network InvestigatorsUK BiLEVE InvestigatorsInternational COPD Genetics Consortium
- Contributors
- Eric A Hoffman (Contributor) - University of Iowa, Radiology
- Resource Type
- Journal article
- Publication Details
- Nature genetics, Vol.49(3), pp.426-432
- Publisher
- United States
- DOI
- 10.1038/ng.3752
- PMID
- 28166215
- PMCID
- PMC5381275
- ISSN
- 1061-4036
- eISSN
- 1546-1718
- Grant note
- R01 HL084323 / NHLBI NIH HHS R01 HL124233 / NHLBI NIH HHS MR/N024842/1 / Medical Research Council MC_PC_12010 / Medical Research Council R01 HL113264 / NHLBI NIH HHS U01 HL089856 / NHLBI NIH HHS R01 HL097163 / NHLBI NIH HHS R01 HL077612 / NHLBI NIH HHS R33 HL120770 / NHLBI NIH HHS K01 HL129039 / NHLBI NIH HHS U01 HL130114 / NHLBI NIH HHS T32 HL007427 / NHLBI NIH HHS U01 HL137880 / NHLBI NIH HHS U01 HL089897 / NHLBI NIH HHS R01 HL089856 / NHLBI NIH HHS P01 HL114501 / NHLBI NIH HHS R01 HL093081 / NHLBI NIH HHS P01 HL092870 / NHLBI NIH HHS MR/N011317/1 / Medical Research Council R01 HL105756 / NHLBI NIH HHS R01 HL126596 / NHLBI NIH HHS R01 HL075478 / NHLBI NIH HHS P30 CA118100 / NCI NIH HHS P01 HL105339 / NHLBI NIH HHS K08 HL097029 / NHLBI NIH HHS S10 OD018526 / NIH HHS G1000861 / Medical Research Council G0902313 / Medical Research Council R01 HL089897 / NHLBI NIH HHS
- Language
- English
- Date published
- 03/2017
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology; Internal Medicine
- Record Identifier
- 9984051562902771
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