Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations
Year: 2019
Type: article
Study design: Observational Study
Abstract: Chronic obstructive pulmonary disease (COPD) is the leading cause of respiratory mortality worldwide. Genetic risk loci provide new insights into disease pathogenesis. We performed a genome-wide association study in 35,735 cases and 222,076 controls from the UK Biobank and additional studies from the International COPD Genetics Consortium. We identified 82 loci associated with P < 5 × 10−8; 47 of these were previously described in association with either COPD or population-based measures of lung function. Of the remaining 35 new loci, 13 were associated with lung function in 79,055 individuals from the SpiroMeta consortium. Using gene expression and regulation data, we identified functional enrichment of COPD risk loci in lung tissue, smooth muscle, and several lung cell types. We found 14 COPD loci shared with either asthma or pulmonary fibrosis. COPD genetic risk loci clustered into groups based on associations with quantitative imaging features and comorbidities. Our analyses provide further support for the genetic susceptibility and heterogeneity of COPD. Genome-wide analysis of chronic obstructive pulmonary disease identifies 82 loci, 35 of which are new. Integration of gene expression and genomic annotation data shows enrichment of signals in lung tissue, smooth muscle and several lung cell types.
Source: Nature Genetics
Authors: Phuwanat Sakornsakolpat, Dmitry Prokopenko, Maxime Lamontagne, Nicola F. Reeve, Anna L. Guyatt, Victoria E. Jackson, Nick Shrine, Dandi Qiao, Traci M. Bartz, Deog Kyeom Kim, Mi Kyeong Lee, Jeanne C. Latourelle, Xingnan Li, Jarrett D. Morrow, Ma’en Obeidat, Annah B. Wyss, Per Bakke, R. Graham Barr, Terri H. Beaty, Steven A. Belinsky, Guy G. Brusselle, James D. Crapo, Kim de Jong, Dawn L. DeMeo, Tasha E. Fingerlin, Sina A. Gharib, Amund Gulsvik, Ian P. Hall, John E. Hokanson, Woo Jin Kim, David A. Lomas, Stephanie J. London, Deborah A. Meyers, George T. O’Connor, Stephen I. Rennard, David A. Schwartz, Pawel Sliwinski, David Sparrow, David P. Strachan, Ruth Tal-Singer, Yohannes Tesfaigzi, Jørgen Vestbo, Judith M. Vonk, Jae-Joon Yim, Xiaobo Zhou, Yohan Bossé, Ani Manichaikul, Lies Lahousse, Edwin K. Silverman, H. Marike Boezen, Louise V. Wain, Martin D. Tobin, Brian D. Hobbs, Michael H. Cho, Nick Shrine, Anna L. Guyatt, Chiara Batini, Jing Hua Zhao, Matthias Wielscher, Understanding Society Scientific Group, Stefan Weiss, Katherine A. Kentistou, James P. Cook, Jennie Hui, Stefan Karrasch, Medea Imboden, Sarah E. Harris, Jonathan Marten, Stefan Enroth, Shona M. Kerr, Ida Surakka, Veronique Vitart, Terho Lehtimäki, Ralf Ewert, Christian Gieger, Georg Homuth, Peter K. Joshi, Claudia Langenberg, Lars Lind, Jian’an Luan, Anubha Mahajan, Alison Murray, David J. Porteous, Rajesh Rawal, Blair H. Smith, Paul R. H. J. Timmers, Olli T. Raitakari, Mika Kähönen, Ozren Polasek, Ulf Gyllensten, Igor Rudan, Ian J. Deary, Nicole M. Probst-Hensch, Holger Schulz, Alan L. James, James F. Wilson, Beate Stubbe, Eleftheria Zeggini, Marjo-Riitta Jarvelin, Nick Wareham, Caroline Hayward, Andrew P. Morris, David P. Strachan, Ian P. Hall, Martin D. Tobin, Louise V. Wain, Alvar Agusti, Wayne Anderson, Nawar Bakerly, Per Bakke, Robert Bals, Kathleen C. Barnes, R. Graham Barr, Terri H. Beaty, Eugene R. Bleecker, H. Marike Boezen, Yohan Bossé, Russell Bowler, Christopher Brightling, Marleen de Bruijne, Peter J. Castaldi, Bartolome Celli, Michael H. Cho, Harvey O. Coxson, James D. Crapo, Ron Crystal, Pim de Jong, Asger Dirksen, Jennifer Dy, Marilyn Foreman, Judith Garcia-Aymerich, Pierre Gevenois, Soumitra Ghosh, Hester Gietema, Amund Gulsvik, Ian P. Hall, Nadia Hansel, Craig P. Hersh, Brian D. Hobbs, Eric Hoffman, Noor Kalsheker, Hans-Ulrich Kauczor, Woo Jin Kim, Deog Kyeom Kim, Tarja Laitinen, Diether Lambrechts, Sang-Do Lee, Augusto A. Litonjua, David A. Lomas, Stephanie J. London, Daan W. Loth, Sharon M. Lutz, David Lynch, William MacNee, Merry-Lynn McDonald, Deborah A. Meyers, John D. Newell, Borge G. Nordestgaard, George T. O’Connor, Ma’en Obeidat, Yeon-Mok Oh, Peter D. Paré, Massimo Pistolesi, Dirkje S. Postma, Milo Puhan, Elizabeth Regan, Stephen S. Rich, Joon Beom Seo, Andrea Short, Edwin K. Silverman, David Sparrow, Berend Stoel, David P. Strachan, Nicola Sverzellati, Ruth Tal-Singer, Gerben ter Riet, Yohannes Tesfaigzi, Martin D. Tobin, Edwin J. R. Van Beek, Bram van Ginneken, Jørgen Vestbo, Claus F. Vogelmeier, Louise V. Wain, Adam Wanner, George Washko, Els Wauters, Emiel F. M. Wouters, Robert P. Young, Loems Zeigler-Heitbrock
Institutions: Brigham and Women's Hospital, Siriraj Hospital, Mahidol University, Massachusetts General Hospital, Institut universitaire de cardiologie et de pneumologie de Québec, University of Leicester, University of Washington, Seoul National University, SNUH SMG-SNU Boramae Medical Center, National Institutes of Health, National Institute of Environmental Health Sciences, Boston University, University of Arizona, University of British Columbia, St. Paul's Hospital, Centre for Heart Lung Innovation, University of Bergen, Columbia University, Johns Hopkins University, Lovelace Respiratory Research Institute, Ghent University Hospital, Erasmus MC, National Jewish Health, University Medical Center Groningen, University of Groningen, University of Colorado Denver, University of Nottingham, National Institute for Health and Care Research, Queen's Medical Centre, Nottingham Biomedical Research Centre, University of Colorado Anschutz, Kangwon National University, University College London, Framingham Heart Study, AstraZeneca (United Kingdom), University of Nebraska Medical Center, VA Boston Healthcare System, St George's, University of London, GlaxoSmithKline (United States), University of Manchester, Université Laval, University of Virginia, Ghent University, Glenfield Hospital, Harvard University, University of Cambridge, MRC Centre for Environment and Health, Imperial College London, Universitätsmedizin Greifswald, The Queen's Medical Research Institute, University of Edinburgh, University of Liverpool, Sir Charles Gairdner Hospital, The University of Western Australia, Helmholtz Munich, German Center for Lung Research, Pathwest Laboratory Medicine, Swiss Tropical and Public Health Institute, University of Basel, Institut und Poliklinik für Arbeits-, Sozial- und Umweltmedizin, Ludwig-Maximilians-Universität München, Western General Hospital, Institute of Genetics and Cancer, MRC Human Genetics Unit, Uppsala University, Science for Life Laboratory, University of Helsinki, Finnish Institute for Health and Welfare, Institute for Molecular Medicine Finland, Fimlab (Finland), University of Tampere, MRC Epidemiology Unit, Centre for Human Genetics, University of Oxford, University of Aberdeen, University of Dundee, University of Münster, Ninewells Hospital, University of Turku, Turku University Hospital, Tampere University Hospital, University of Split, Wellcome Sanger Institute, Oulu University Hospital, Brunel University of London, University of Oulu, Hospital Clínic de Barcelona, Consorci Institut D'Investigacions Biomediques August Pi I Sunyer, Universitat de Barcelona, University of North Carolina at Chapel Hill, Manchester Academic Health Science Centre, Salford Royal NHS Foundation Trust, Saarland University, University of Copenhagen, Weill Cornell Medicine, University Medical Center Utrecht, Herlev Hospital, Gentofte Hospital, Northeastern University, Morehouse School of Medicine, Universitat Pompeu Fabra, Barcelona Institute for Global Health, Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, Université Libre de Bruxelles, Erasmus Hospital, Maastricht University Medical Centre, University of Iowa, Heidelberg University, KU Leuven, Asan Medical Center, University of Ulsan, University of Rochester Medicine, Golisano Children's Hospital, Harvard Pilgrim Health Care, University of Alabama at Birmingham, Copenhagen University Hospital, Azienda Ospedaliero-Universitaria Careggi, University of Zurich, Leiden University Medical Center, University of Parma, Amsterdam UMC Location University of Amsterdam, University of Amsterdam, Radboud University Medical Center, Philipps University of Marburg, University of Miami, University of Auckland
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $12,690
Awards: Role of Genetics in Idiopathic Pulmonary Fibrosis (IPF), Identifying Genetic Determinants of Severe, Early-Onset COPD, G2588136129, G2608539557, Large-scale genomic epidemiology approaches to study the natural history of lung function and COPD, Identifying functional variants in COPD GWAS loci, G31787379, Network-based Methods for Understanding Genetic Determinants and Epistasis in COPD, Systems Biology of Airway Disease, NIHR Senior Investigator Award, Genetic Determinants of COPD in Diverse Ethnic Groups, (2 of 2) Genetic Epidemiology of COPD, G4405771736, G4641403149, Interstitial Lung Abnormalities: Defining the Phenotype, Causes, and Consequences., G5067462658, Functional Genetics of COPD, (2 of 2) Genetic Epidemiology of COPD, G5850737185, Multi-omic Subtyping of Chronic Obstructive Pulmonary Disease, Functional Genetics in Idiopathic Pulmonary Fibrosis, G6823029834, A genome-wide association study of non-pathological cognitive ageing, G7392658454, G8330560607, G8334119512, Multi-Disciplinary Research Training in Respiratory Disease, Genetic and Genomic Characterization of the Occurrence and Progression of Interstitial Lung Abnormalities
OpenAlex ID: W2917263971