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New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries.
Shrine, Nick; Guyatt, Anna L; Erzurumluoglu, A Mesut; Jackson, Victoria E; Hobbs, Brian D; Melbourne, Carl A; Batini, Chiara; Fawcett, Katherine A; Song, Kijoung; Sakornsakolpat, Phuwanat; Li, Xingnan; Boxall, Ruth; Reeve, Nicola F; Obeidat, Ma'en; Zhao, Jing Hua; Wielscher, Matthias; Weiss, Stefan; Kentistou, Katherine A; Cook, James P; Sun, Benjamin B; Zhou, Jian; Hui, Jennie; Karrasch, Stefan; Imboden, Medea; Harris, Sarah E; Marten, Jonathan; Enroth, Stefan; Kerr, Shona M; Surakka, Ida; Vitart, Veronique; Lehtimäki, Terho; Allen, Richard J; Bakke, Per S; Beaty, Terri H; Bleecker, Eugene R; Bossé, Yohan; Brandsma, Corry-Anke; Chen, Zhengming; Crapo, James D; Danesh, John; DeMeo, Dawn L; Dudbridge, Frank; Ewert, Ralf; Gieger, Christian; Gulsvik, Amund; Hansell, Anna L; Hao, Ke; Hoffman, Joshua D; Hokanson, John E; Homuth, Georg.
Afiliação
  • Shrine N; Department of Health Sciences, University of Leicester, Leicester, UK.
  • Guyatt AL; Department of Health Sciences, University of Leicester, Leicester, UK.
  • Erzurumluoglu AM; Department of Health Sciences, University of Leicester, Leicester, UK.
  • Jackson VE; Department of Health Sciences, University of Leicester, Leicester, UK.
  • Hobbs BD; Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
  • Melbourne CA; Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia.
  • Batini C; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
  • Fawcett KA; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA.
  • Song K; Department of Health Sciences, University of Leicester, Leicester, UK.
  • Sakornsakolpat P; Department of Health Sciences, University of Leicester, Leicester, UK.
  • Li X; Department of Health Sciences, University of Leicester, Leicester, UK.
  • Boxall R; Target Sciences, GlaxoSmithKline, Collegeville, PA, USA.
  • Reeve NF; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
  • Obeidat M; Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
  • Zhao JH; Division of Genetics, Genomics and Precision Medicine, Department of Medicine, University of Arizona, Tucson, AZ, USA.
  • Wielscher M; Nuffield Department of Population Health, University of Oxford, Oxford, UK.
  • Weiss S; Medical Research Council Population Health Research Unit, University of Oxford, Oxford, UK.
  • Kentistou KA; Department of Health Sciences, University of Leicester, Leicester, UK.
  • Cook JP; The University of British Columbia Centre for Heart Lung Innovation, St Paul's Hospital, Vancouver, British Columbia, Canada.
  • Sun BB; Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
  • Zhou J; Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment & Health, School of Public Health, Imperial College London, London, UK.
  • Hui J; Interfaculty Institute for Genetics and Functional Genomics, Department of Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
  • Karrasch S; Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.
  • Imboden M; Centre for Cardiovascular Sciences, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.
  • Harris SE; Department of Biostatistics, University of Liverpool, Liverpool, UK.
  • Marten J; MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
  • Enroth S; Flatiron Institute, Simons Foundation, New York, NY, USA.
  • Kerr SM; Busselton Population Medical Research Institute, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.
  • Surakka I; School of Population Health, The University of Western Australia, Crawley, Western Australia, Australia.
  • Vitart V; PathWest Laboratory Medicine of WA, Sir Charles Gairdner Hospital, Crawley, Western Australia, Australia.
  • Lehtimäki T; School of Pathology and Laboratory Medicine, The University of Western Australia, Crawley, Western Australia, Australia.
  • Allen RJ; Institute of Epidemiology, Helmholtz Zentrum Muenchen-German Research Center for Environmental Health, Neuherberg, Germany.
  • Bakke PS; Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, Ludwig-Maximilians-Universität, Munich, Germany.
  • Beaty TH; Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research (DZL), Munich, Germany.
  • Bleecker ER; Swiss Tropical and Public Health Institute, Basel, Switzerland.
  • Bossé Y; University of Basel, Basel, Switzerland.
  • Brandsma CA; Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
  • Chen Z; Centre for Genomic and Experimental Medicine, Institute of Genetics & Molecular Medicine, University of Edinburgh, Edinburgh, UK.
  • Crapo JD; Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
  • Danesh J; Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala Universitet, Uppsala, Sweden.
  • DeMeo DL; Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
  • Dudbridge F; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
  • Ewert R; The National Institute for Health and Welfare (THL), Helsinki, Finland.
  • Gieger C; Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
  • Gulsvik A; Department of Clinical Chemistry, Fimlab Laboratories, and Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland.
  • Hansell AL; Department of Health Sciences, University of Leicester, Leicester, UK.
  • Hao K; Department of Clinical Science, University of Bergen, Bergen, Norway.
  • Hoffman JD; Department of Epidemiology, Johns Hopkins University School of Public Health, Baltimore, MD, USA.
  • Hokanson JE; Division of Genetics, Genomics and Precision Medicine, Department of Medicine, University of Arizona, Tucson, AZ, USA.
  • Homuth G; Department of Molecular Medicine, Laval University, Québec, Canada.
Nat Genet ; 51(3): 481-493, 2019 03.
Article em En | MEDLINE | ID: mdl-30804560
ABSTRACT
Reduced lung function predicts mortality and is key to the diagnosis of chronic obstructive pulmonary disease (COPD). In a genome-wide association study in 400,102 individuals of European ancestry, we define 279 lung function signals, 139 of which are new. In combination, these variants strongly predict COPD in independent populations. Furthermore, the combined effect of these variants showed generalizability across smokers and never smokers, and across ancestral groups. We highlight biological pathways, known and potential drug targets for COPD and, in phenome-wide association studies, autoimmune-related and other pleiotropic effects of lung function-associated variants. This new genetic evidence has potential to improve future preventive and therapeutic strategies for COPD.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Predisposição Genética para Doença / Doença Pulmonar Obstrutiva Crônica / Pulmão Tipo de estudo: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Nat Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Reino Unido
Texto completo
Imprimir
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PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Predisposição Genética para Doença / Doença Pulmonar Obstrutiva Crônica / Pulmão Tipo de estudo: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Nat Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Reino Unido