Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations
Sakornsakolpat, Phuwanat (författare)
Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA;Mahidol Univ, Dept Med, Fac Med, Siriraj Hosp, Bangkok, Thailand
Prokopenko, Dmitry (författare)
Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA;Massachusetts Gen Hosp, Dept Neurol, Genet & Aging Res Unit, Boston, MA 02114 USA
Lamontagne, Maxime (författare)
Inst Univ Cardiol & Pneumol Quebec, Quebec City, PQ, Canada
Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA
Bartz, Traci M. (författare)
Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA;Univ Washington, Dept Med, Seattle, WA 98195 USA;Univ Washington, Dept Biostat, Seattle, WA 98195 USA
Kim, Deog Kyeom (författare)
Seoul Natl Univ, Coll Med, SMG SNU Boramae Med Ctr, Seoul, South Korea
Lee, Mi Kyeong (författare)
NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Raleigh, NC USA
Latourelle, Jeanne C. (författare)
Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA
Li, Xingnan (författare)
Univ Arizona, Dept Med, Tucson, AZ USA
Morrow, Jarrett D. (författare)
Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA
Obeidat, Ma'en (författare)
Univ British Columbia, Ctr Heart Lung Innovat, St Pauls Hosp, Vancouver, BC, Canada
Wyss, Annah B. (författare)
NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Raleigh, NC USA
Bakke, Per (författare)
Univ Bergen, Dept Clin Sci, Bergen, Norway
Barr, R. Graham (författare)
Columbia Univ, Dept Med, Coll Phys & Surg, New York, NY USA;Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY USA
Natl Jewish Hlth, Div Pulm & Crit Care Med, Dept Med, Denver, CO USA
de Jong, Kim (författare)
Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands;Univ Groningen, Univ Med Ctr Groningen, GRIAC, Groningen, Netherlands
DeMeo, Dawn L. (författare)
Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA;Brigham & Womens Hosp, Div Pulm & Crit Care Med, 75 Francis St, Boston, MA 02115 USA
Fingerlin, Tasha E. (författare)
Natl Jewish Hlth, Ctr Genes Environm & Hlth, Denver, CO USA;Univ Colorado Denver, Dept Biostat & Informat, Aurora, CO USA
Gharib, Sina A. (författare)
Univ Washington, Computat Med Core, Ctr Lung Biol, UW Med Sleep Ctr,Dept Med, Seattle, WA 98195 USA
Gulsvik, Amund (författare)
Univ Bergen, Dept Clin Sci, Bergen, Norway
Hall, Ian P. (författare)
Univ Nottingham, Div Resp Med, Queens Med Ctr, Nottingham, England;Nottingham Biomed Res Ctr, Natl Inst Hlth Res, Nottingham, England
Hokanson, John E. (författare)
Univ Colorado, Dept Epidemiol, Anschutz Med Campus, Aurora, CO USA
Kim, Woo Jin (författare)
Kangwon Natl Univ, Dept Internal Med, Sch Med, Chunchon, South Korea;Kangwon Natl Univ, Environm Hlth Ctr, Chunchon, South Korea
Lomas, David A. (författare)
UCL, UCL Resp, London, England
London, Stephanie J. (författare)
NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Raleigh, NC USA
Meyers, Deborah A. (författare)
Univ Arizona, Dept Med, Tucson, AZ USA
O'Connor, George T. (författare)
Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA;Boston Univ, Sch Med, Dept Med, Pulm Ctr, Boston, MA 02118 USA
Rennard, Stephen, I (författare)
Univ Nebraska Med Ctr, Pulm Crit Care Sleep & Allergy Div, Omaha, NE USA;AstraZeneca, Clin Discovery Unit, Cambridge, England
Schwartz, David A. (författare)
Univ Colorado Denver, Dept Med, Sch Med, Aurora, CO USA;Univ Colorado Denver, Sch Med, Dept Immunol, Aurora, CO USA
Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA;Brigham & Womens Hosp, Div Pulm & Crit Care Med, 75 Francis St, Boston, MA 02115 USA
Boezen, H. Marike (författare)
Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands;Univ Groningen, Univ Med Ctr Groningen, GRIAC, Groningen, Netherlands
Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA;Brigham & Womens Hosp, Div Pulm & Crit Care Med, 75 Francis St, Boston, MA 02115 USA
Cho, Michael H. (författare)
Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA;Brigham & Womens Hosp, Div Pulm & Crit Care Med, 75 Francis St, Boston, MA 02115 USA
Univ Edinburgh, Ctr Global Hlth Res, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland;Univ Edinburgh, Ctr Cardiovasc Sci, Queens Med Res Inst, Edinburgh, Midlothian, Scotland
Cook, James P. (författare)
Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England
Hui, Jennie (författare)
Sir Charles Gairdner Hosp, Busselton Populat Med Res Inst, Nedlands, WA, Australia;Univ Western Australia, Sch Populat Hlth, Crawley, WA, Australia;Sir Charles Gairdner Hosp, PathWest Lab Med WA, Crawley, WA, Australia;Univ Western Australia, Sch Pathol & Lab Med, Crawley, WA, Australia
Karrasch, Stefan (författare)
German Res Ctr Environm Hlth, Inst Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany;Ludwig Maximilians Univ Munchen, Inst & Outpatient Clin Occupat Social & Environm, Munich, Germany;German Ctr Lung Res DZL, Comprehens Pneumol Ctr Munich, Munich, Germany
Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland;Univ Edinburgh, Western Gen Hosp, Ctr Genom & Expt Med, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland
Marten, Jonathan (författare)
Univ Edinburgh, Med Res Council, Inst Genet & Mol Med, Human Genet Unit, Edinburgh, Midlothian, Scotland
Enroth, Stefan, 1976- (författare)
Uppsala universitet,Science for Life Laboratory, SciLifeLab,Medicinsk genetik och genomik
Kerr, Shona M. (författare)
Univ Edinburgh, Med Res Council, Inst Genet & Mol Med, Human Genet Unit, Edinburgh, Midlothian, Scotland
Surakka, Ida (författare)
Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland;Natl Inst Hlth & Welf THL, Helsinki, Finland
Vitart, Veronique (författare)
Univ Edinburgh, Med Res Council, Inst Genet & Mol Med, Human Genet Unit, Edinburgh, Midlothian, Scotland
Lehtimaki, Terho (författare)
Univ Tampere, Dept Clin Chem, Fimlab Labs, Fac Med & Life Sci, Tampere, Finland;Univ Tampere, Finnish Cardiovasc Res Ctr Tampere, Fac Med & Life Sci, Tampere, Finland
Ewert, Ralf (författare)
Univ Med Greifswald, Dept Internal Med B Cardiol Intens Care Pulm Med, Greifswald, Germany
Gieger, Christian (författare)
German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Inst Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany
Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland;Univ Edinburgh, Western Gen Hosp, Ctr Genom & Expt Med, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland
Rawal, Rajesh (författare)
German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Inst Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany;Univ Munster, Inst Epidemiol & Social Med, Munster, Germany
Smith, Blair H. (författare)
Univ Dundee, Div Populat Hlth & Genom, Ninewells Hosp & Med Sch, Dundee, Scotland
Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku, Finland;Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland
Kahonen, Mika (författare)
Univ Tampere, Finnish Cardiovasc Res Ctr Tampere, Fac Med & Life Sci, Tampere, Finland;Univ Tampere, Dept Clin Physiol, Tampere Univ Hosp, Tampere, Finland
German Res Ctr Environm Hlth, Inst Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany;German Ctr Lung Res DZL, Comprehens Pneumol Ctr Munich, Munich, Germany
James, Alan L. (författare)
Sir Charles Gairdner Hosp, Busselton Populat Med Res Inst, Nedlands, WA, Australia;Sir Charles Gairdner Hosp, Dept Pulm Physiol & Sleep Med, Nedlands, WA, Australia;Univ Western Australia, Sch Med & Pharmacol, Crawley, WA, Australia
Wilson, James F. (författare)
Univ Edinburgh, Ctr Global Hlth Res, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland;Univ Edinburgh, Med Res Council, Inst Genet & Mol Med, Human Genet Unit, Edinburgh, Midlothian, Scotland
Stubbe, Beate (författare)
Univ Med Greifswald, Dept Internal Med B Cardiol Intens Care Pulm Med, Greifswald, Germany
Zeggini, Eleftheria (författare)
Wellcome Sanger Inst, Hinxton, England;German Res Ctr Environm Hlth, Inst Translat Genom, Helmholtz Zentrum Munchen, Neuherberg, Germany
Jarvelin, Marjo-Riitta (författare)
Imperial Coll London, Dept Epidemiol & Biostat, MRC PHE Ctr Environm & Hlth, Sch Publ Hlth, London, England;Univ Oulu, Ctr Life Course Hlth Res, Fac Med, Oulu, Finland;Univ Oulu, Bioctr Oulu, Oulu, Finland;Oulu Univ Hosp, OYS, Unit Primary Hlth Care, Oulu, Finland;Brunel Univ London, Dept Life Sci, Coll Hlth & Life Sci, Uxbridge, Middx, England
Wareham, Nick (författare)
Univ Cambridge, Sch Clin Med, Med Res Council, Epidemiol Unit, Cambridge, England
Hayward, Caroline (författare)
Univ Edinburgh, Med Res Council, Inst Genet & Mol Med, Human Genet Unit, Edinburgh, Midlothian, Scotland
Morris, Andrew P. (författare)
Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England
Univ Libre Bruxelles, Hop Erasme, Dept Radiol, Brussels, Belgium
Ghosh, Soumitra (författare)
GlaxoSmithKline R&D, Collegeville, PA USA
Gietema, Hester (författare)
Maastricht Univ, Med Ctr, Dept Radiol, Maastricht, Netherlands
Hansel, Nadia (författare)
Johns Hopkins Univ, Dept Med, Baltimore, MD USA
Hersh, Craig P. (författare)
Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA;Brigham & Womens Hosp, Div Pulm & Crit Care Med, 75 Francis St, Boston, MA 02115 USA
Hoffman, Eric (författare)
Univ Iowa, Dept Radiol, Iowa City, IA 52242 USA
Kalsheker, Noor (författare)
Univ Nottingham, Sch Life Sci, Nottingham, England
Univ Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Birmingham, AL USA
Newell, John D. (författare)
Univ Iowa, Dept Radiol, Iowa City, IA 52242 USA
Nordestgaard, Borge G. (författare)
Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Clin Biochem & Copenhagen Gen Populat Study, Herlev, Denmark;Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark
Oh, Yeon-Mok (författare)
Univ Ulsan Coll Med, Dept Pulm & Crit Care Med, Asan Med Ctr, Seoul, South Korea;Univ Ulsan Coll Med, Clin Res Ctr Chron Obstruct Airway Dis, Seoul, South Korea
Pare, Peter D. (författare)
Univ British Columbia, Ctr Heart Lung Innovat, St Pauls Hosp, Vancouver, BC, Canada;Univ British Columbia, St Pauls Hosp, Inst Heart & Lung Hlth, Dept Med, Vancouver, BC, Canada
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 x 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.
Ämnesord
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Respiratory Medicine and Allergy (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Lungmedicin och allergi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)
MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine (hsv//eng)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)