New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-02-25

AUTHORS

Nick Shrine, Anna L. Guyatt, A. Mesut Erzurumluoglu, Victoria E. Jackson, Brian D. Hobbs, Carl A. Melbourne, Chiara Batini, Katherine A. Fawcett, Kijoung Song, Phuwanat Sakornsakolpat, Xingnan Li, Ruth Boxall, Nicola F. Reeve, Ma’en Obeidat, Jing Hua Zhao, Matthias Wielscher, Stefan Weiss, Katherine A. Kentistou, James P. Cook, Benjamin B. Sun, Jian Zhou, Jennie Hui, Stefan Karrasch, Medea Imboden, Sarah E Harris, Jonathan Marten, Stefan Enroth, Shona M. Kerr, Ida Surakka, Veronique Vitart, Terho Lehtimäki, Richard J. Allen, Per S. Bakke, Terri H. Beaty, Eugene R. Bleecker, Yohan Bossé, Corry-Anke Brandsma, Zhengming Chen, James D. Crapo, John Danesh, Dawn L. DeMeo, Frank Dudbridge, Ralf Ewert, Christian Gieger, Amund Gulsvik, Anna L. Hansell, Ke Hao, Joshua D. Hoffman, John E. Hokanson, Georg Homuth, Peter K. Joshi, Philippe Joubert, Claudia Langenberg, Xuan Li, Liming Li, Kuang Lin, Lars Lind, Nicholas Locantore, Jian’an Luan, Anubha Mahajan, Joseph C. Maranville, Alison Murray, David C. Nickle, Richard Packer, Margaret M. Parker, Megan L. Paynton, David J. Porteous, Dmitry Prokopenko, Dandi Qiao, Rajesh Rawal, Heiko Runz, Ian Sayers, Don D Sin, Blair H Smith, María Soler Artigas, David Sparrow, Ruth Tal-Singer, Paul R. H. J. Timmers, Maarten Van den Berge, John C. Whittaker, Prescott G. Woodruff, Laura M. Yerges-Armstrong, Olga G. Troyanskaya, Olli T. Raitakari, Mika Kähönen, Ozren Polašek, 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, Edwin K. Silverman, Caroline Hayward, Andrew P. Morris, Adam S. Butterworth, Robert A. Scott, Robin G. Walters, Deborah A. Meyers, Michael H. Cho, David P. Strachan, Ian P. Hall, Martin D. Tobin, Louise V. Wain

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. More... »

PAGES

481-493

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  • Journal

    TITLE

    Nature Genetics

    ISSUE

    3

    VOLUME

    51

    Author Affiliations

  • Department of Health Sciences, University of Leicester, Leicester, UK
  • Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia
  • Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Boston, MA, USA
  • Target Sciences, GlaxoSmithKline, Collegeville, PA, USA
  • Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
  • Division of Genetics, Genomics and Precision Medicine, Department of Medicine, University of Arizona, Tucson, AZ, USA
  • Medical Research Council Population Health Research Unit, University of Oxford, Oxford, UK
  • The University of British Columbia Centre for Heart Lung Innovation, St Paul’s Hospital, Vancouver, British Columbia, Canada
  • Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
  • Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment & Health, School of Public Health, Imperial College London, London, UK
  • Interfaculty Institute for Genetics and Functional Genomics, Department of Functional Genomics, University Medicine Greifswald, Greifswald, Germany
  • Centre for Cardiovascular Sciences, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK
  • Department of Biostatistics, University of Liverpool, Liverpool, UK
  • MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
  • Flatiron Institute, Simons Foundation, New York, NY, USA
  • School of Pathology and Laboratory Medicine, The University of Western Australia, Crawley, Western Australia, Australia
  • Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research (DZL), Munich, Germany
  • University of Basel, Basel, Switzerland
  • Centre for Genomic and Experimental Medicine, Institute of Genetics & Molecular Medicine, University of Edinburgh, Edinburgh, UK
  • Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
  • Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala Universitet, Uppsala, Sweden
  • The National Institute for Health and Welfare (THL), Helsinki, Finland
  • Department of Clinical Chemistry, Fimlab Laboratories, and Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
  • Department of Clinical Science, University of Bergen, Bergen, Norway
  • Department of Epidemiology, Johns Hopkins University School of Public Health, Baltimore, MD, USA
  • Institut Universitaire de Cardiologie et de Pneumologie de Québec, Laval University, Québec, Canada
  • University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, GRIAC Research Institute, University of Groningen, Groningen, The Netherlands
  • Nuffield Department of Population Health, University of Oxford, Oxford, UK
  • Division of Pulmonary, Critical Care and Sleep Medicine, National Jewish Health, Denver, CO, USA
  • NIHR Blood and Transplant Research Unit in Donor Health and Genomics, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
  • Department of Internal Medicine B - Cardiology, Intensive Care, Pulmonary Medicine and Infectious Diseases, University Medicine Greifswald, Greifswald, Germany
  • Research Unit of Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum Muenchen – German Research Center for Environmental Health, Neuherberg, Germany
  • Imperial College Healthcare NHS Trust, St Mary’s Hospital, London, UK
  • Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
  • Department of Epidemiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
  • Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK
  • Department of Molecular Biology, Medical Biochemistry, and Pathology, Laval University, Québec, Canada
  • MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, UK
  • Department of Epidemiology & Biostatistics, Peking University Health Science Center, Beijing, China
  • Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden
  • GSK R&D, Collegeville, PA, USA
  • Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
  • MRL, Merck & Co., Inc, Kenilworth, NJ, USA
  • The Institute of Medical Sciences, Aberdeen Biomedical Imaging Centre, University of Aberdeen, Aberdeen, UK
  • Gossamer Bio, San Diego, CA, USA
  • Channing Division of Network Medicine, Brigham and Women’s Hospital, Boston, MA, USA
  • Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany
  • Division of Respiratory Medicine and NIHR-Nottingham Biomedical Research Centre, University of Nottingham, Nottingham, UK
  • Respiratory Division, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
  • Division of Population Health and Genomics, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK
  • Biomedical Network Research Centre on Mental Health (CIBERSAM), Instituto de Salud Carlos III, Barcelona, Spain
  • Department of Medicine, Boston University School of Medicine, Boston, MA, USA
  • University of Groningen, University Medical Center Groningen, Department of Pulmonology, GRIAC Research Institute, University of Groningen, Groningen, The Netherlands
  • Target Sciences - R&D, GSK Medicines Research Centre, Stevenage, UK
  • UCSF Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California, San Francisco, CA, USA
  • Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA
  • Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland
  • Department of Clinical Physiology, Tampere University Hospital, and Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
  • University of Split School of Medicine, Split, Croatia
  • Department of Psychology, University of Edinburgh, Edinburgh, UK
  • School of Medicine and Pharmacology, The University of Western Australia, Crawley, Western Australia, Australia
  • Institute of Translational Genomics, Helmholtz Zentrum Muenchen – German Research Center for Environmental Health, Neuherberg, Germany
  • Department of Life Sciences, College of Health and Life Sciences, Brunel University London, Uxbridge, UK
  • Population Health Research Institute, St George’s, University of London, London, UK
  • National Institute for Health Research, Leicester Respiratory Biomedical Research Centre, Glenfield Hospital, Leicester, UK
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41588-018-0321-7

    DOI

    http://dx.doi.org/10.1038/s41588-018-0321-7

    DIMENSIONS

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    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30804560


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