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


Journal

Nature genetics
ISSN: 1546-1718
Titre abrégé: Nat Genet
Pays: United States
ID NLM: 9216904

Informations de publication

Date de publication:
03 2019
Historique:
received: 08 06 2018
accepted: 27 11 2018
pubmed: 26 2 2019
medline: 25 4 2019
entrez: 27 2 2019
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 30804560
doi: 10.1038/s41588-018-0321-7
pii: 10.1038/s41588-018-0321-7
pmc: PMC6397078
mid: NIHMS1514965
doi:

Types de publication

Journal Article Meta-Analysis Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

481-493

Subventions

Organisme : NHLBI NIH HHS
ID : R01 HL113264
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL089897
Pays : United States
Organisme : Wellcome Trust
ID : 212946/Z/18/Z
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RG/13/13/30194
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12026/2
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12015/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N01104X/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00017/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : G1000861
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_U137686851
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_14135
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/F019394/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/K026992/1
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : U01 HL089897
Pays : United States
Organisme : Medical Research Council
ID : MR/N01104X/2
Pays : United Kingdom
Organisme : Medical Research Council
ID : G1001799
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0700704
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : R01 HL111024
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL089856
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL135142
Pays : United States
Organisme : Medical Research Council
ID : MC_PC_12010
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00007/10
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : K08 HL136928
Pays : United States
Organisme : NHLBI NIH HHS
ID : K01 HL129039
Pays : United States
Organisme : Medical Research Council
ID : 1508647
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/S003762/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N011317/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_13049
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 202849/Z/16/Z
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RG/18/13/33946
Pays : United Kingdom

Commentaires et corrections

Type : ErratumIn
Type : ErratumIn

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Auteurs

Nick Shrine (N)

Department of Health Sciences, University of Leicester, Leicester, UK.

Anna L Guyatt (AL)

Department of Health Sciences, University of Leicester, Leicester, UK.

A Mesut Erzurumluoglu (AM)

Department of Health Sciences, University of Leicester, Leicester, UK.

Victoria E Jackson (VE)

Department of Health Sciences, University of Leicester, Leicester, UK.
Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia.

Brian D Hobbs (BD)

Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA.

Carl A Melbourne (CA)

Department of Health Sciences, University of Leicester, Leicester, UK.

Chiara Batini (C)

Department of Health Sciences, University of Leicester, Leicester, UK.

Katherine A Fawcett (KA)

Department of Health Sciences, University of Leicester, Leicester, UK.

Kijoung Song (K)

Target Sciences, GlaxoSmithKline, Collegeville, PA, USA.

Phuwanat Sakornsakolpat (P)

Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

Xingnan Li (X)

Division of Genetics, Genomics and Precision Medicine, Department of Medicine, University of Arizona, Tucson, AZ, USA.

Ruth Boxall (R)

Nuffield Department of Population Health, University of Oxford, Oxford, UK.
Medical Research Council Population Health Research Unit, University of Oxford, Oxford, UK.

Nicola F Reeve (NF)

Department of Health Sciences, University of Leicester, Leicester, UK.

Ma'en Obeidat (M)

The University of British Columbia Centre for Heart Lung Innovation, St Paul's Hospital, Vancouver, British Columbia, Canada.

Jing Hua Zhao (JH)

Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.

Matthias Wielscher (M)

Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment & Health, School of Public Health, Imperial College London, London, UK.

Stefan Weiss (S)

Interfaculty Institute for Genetics and Functional Genomics, Department of Functional Genomics, University Medicine Greifswald, Greifswald, Germany.

Katherine A Kentistou (KA)

Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.
Centre for Cardiovascular Sciences, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.

James P Cook (JP)

Department of Biostatistics, University of Liverpool, Liverpool, UK.

Benjamin B Sun (BB)

MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.

Jian Zhou (J)

Flatiron Institute, Simons Foundation, New York, NY, USA.

Jennie Hui (J)

Busselton Population Medical Research Institute, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.
School of Population Health, The University of Western Australia, Crawley, Western Australia, Australia.
PathWest Laboratory Medicine of WA, Sir Charles Gairdner Hospital, Crawley, Western Australia, Australia.
School of Pathology and Laboratory Medicine, The University of Western Australia, Crawley, Western Australia, Australia.

Stefan Karrasch (S)

Institute of Epidemiology, Helmholtz Zentrum Muenchen-German Research Center for Environmental Health, Neuherberg, Germany.
Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, Ludwig-Maximilians-Universität, Munich, Germany.
Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research (DZL), Munich, Germany.

Medea Imboden (M)

Swiss Tropical and Public Health Institute, Basel, Switzerland.
University of Basel, Basel, Switzerland.

Sarah E Harris (SE)

Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
Centre for Genomic and Experimental Medicine, Institute of Genetics & Molecular Medicine, University of Edinburgh, Edinburgh, UK.

Jonathan Marten (J)

Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.

Stefan Enroth (S)

Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala Universitet, Uppsala, Sweden.

Shona M Kerr (SM)

Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.

Ida Surakka (I)

Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
The National Institute for Health and Welfare (THL), Helsinki, Finland.

Veronique Vitart (V)

Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.

Terho Lehtimäki (T)

Department of Clinical Chemistry, Fimlab Laboratories, and Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland.

Richard J Allen (RJ)

Department of Health Sciences, University of Leicester, Leicester, UK.

Per S Bakke (PS)

Department of Clinical Science, University of Bergen, Bergen, Norway.

Terri H Beaty (TH)

Department of Epidemiology, Johns Hopkins University School of Public Health, Baltimore, MD, USA.

Eugene R Bleecker (ER)

Division of Genetics, Genomics and Precision Medicine, Department of Medicine, University of Arizona, Tucson, AZ, USA.

Yohan Bossé (Y)

Department of Molecular Medicine, Laval University, Québec, Canada.
Institut Universitaire de Cardiologie et de Pneumologie de Québec, Laval University, Québec, Canada.

Corry-Anke Brandsma (CA)

University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, GRIAC Research Institute, University of Groningen, Groningen, The Netherlands.

Zhengming Chen (Z)

Nuffield Department of Population Health, University of Oxford, Oxford, UK.

James D Crapo (JD)

National Jewish Health, Denver, CO, USA.
Division of Pulmonary, Critical Care and Sleep Medicine, National Jewish Health, Denver, CO, USA.

John Danesh (J)

MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
British Heart Foundation Cambridge Centre of Excellence, Division of Cardiovascular Medicine, Addenbrooke's Hospital, Cambridge, UK.
Department of Human Genetics, Wellcome Trust Sanger Institute, Cambridge, UK.
NIHR Blood and Transplant Research Unit in Donor Health and Genomics, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.

Dawn L DeMeo (DL)

Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA.

Frank Dudbridge (F)

Department of Health Sciences, University of Leicester, Leicester, UK.

Ralf Ewert (R)

Department of Internal Medicine B - Cardiology, Intensive Care, Pulmonary Medicine and Infectious Diseases, University Medicine Greifswald, Greifswald, Germany.

Christian Gieger (C)

Research Unit of Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum Muenchen - German Research Center for Environmental Health, Neuherberg, Germany.

Amund Gulsvik (A)

Department of Clinical Science, University of Bergen, Bergen, Norway.

Anna L Hansell (AL)

Centre for Environmental Health & Sustainability, University of Leicester, Leicester, UK.
UK Small Area Health Statistics Unit, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.
Imperial College Healthcare NHS Trust, St Mary's Hospital, London, UK.

Ke Hao (K)

Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Joshua D Hoffman (JD)

Target Sciences, GlaxoSmithKline, Collegeville, PA, USA.

John E Hokanson (JE)

Department of Epidemiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

Georg Homuth (G)

Interfaculty Institute for Genetics and Functional Genomics, Department of Functional Genomics, University Medicine Greifswald, Greifswald, Germany.

Peter K Joshi (PK)

Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.

Philippe Joubert (P)

Institut Universitaire de Cardiologie et de Pneumologie de Québec, Laval University, Québec, Canada.
Department of Molecular Biology, Medical Biochemistry, and Pathology, Laval University, Québec, Canada.

Claudia Langenberg (C)

MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, UK.

Xuan Li (X)

The University of British Columbia Centre for Heart Lung Innovation, St Paul's Hospital, Vancouver, British Columbia, Canada.

Liming Li (L)

Department of Epidemiology & Biostatistics, Peking University Health Science Center, Beijing, China.

Kuang Lin (K)

Nuffield Department of Population Health, University of Oxford, Oxford, UK.

Lars Lind (L)

Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden.

Nicholas Locantore (N)

GSK R&D, Collegeville, PA, USA.

Jian'an Luan (J)

MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, UK.

Anubha Mahajan (A)

Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.

Joseph C Maranville (JC)

MRL, Merck & Co., Inc, Kenilworth, NJ, USA.

Alison Murray (A)

The Institute of Medical Sciences, Aberdeen Biomedical Imaging Centre, University of Aberdeen, Aberdeen, UK.

David C Nickle (DC)

MRL, Merck & Co., Inc, Kenilworth, NJ, USA.
Gossamer Bio, San Diego, CA, USA.

Richard Packer (R)

Department of Health Sciences, University of Leicester, Leicester, UK.

Margaret M Parker (MM)

Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.

Megan L Paynton (ML)

Department of Health Sciences, University of Leicester, Leicester, UK.

David J Porteous (DJ)

Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
Centre for Genomic and Experimental Medicine, Institute of Genetics & Molecular Medicine, University of Edinburgh, Edinburgh, UK.

Dmitry Prokopenko (D)

Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.

Dandi Qiao (D)

Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.

Rajesh Rawal (R)

Research Unit of Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum Muenchen - German Research Center for Environmental Health, Neuherberg, Germany.
Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany.

Heiko Runz (H)

MRL, Merck & Co., Inc, Kenilworth, NJ, USA.

Ian Sayers (I)

Division of Respiratory Medicine and NIHR-Nottingham Biomedical Research Centre, University of Nottingham, Nottingham, UK.

Don D Sin (DD)

The University of British Columbia Centre for Heart Lung Innovation, St Paul's Hospital, Vancouver, British Columbia, Canada.
Respiratory Division, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.

Blair H Smith (BH)

Division of Population Health and Genomics, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.

María Soler Artigas (M)

Psychiatric Genetics Unit, Group of Psychiatry, Mental Health and Addiction, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.
Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
Biomedical Network Research Centre on Mental Health (CIBERSAM), Instituto de Salud Carlos III, Barcelona, Spain.

David Sparrow (D)

VA Boston Healthcare System, Boston, MA, USA.
Department of Medicine, Boston University School of Medicine, Boston, MA, USA.

Ruth Tal-Singer (R)

GSK R&D, Collegeville, PA, USA.

Paul R H J Timmers (PRHJ)

Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.

Maarten Van den Berge (M)

University of Groningen, University Medical Center Groningen, Department of Pulmonology, GRIAC Research Institute, University of Groningen, Groningen, The Netherlands.

John C Whittaker (JC)

Target Sciences - R&D, GSK Medicines Research Centre, Stevenage, UK.

Prescott G Woodruff (PG)

UCSF Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California, San Francisco, CA, USA.

Laura M Yerges-Armstrong (LM)

Target Sciences, GlaxoSmithKline, Collegeville, PA, USA.

Olga G Troyanskaya (OG)

Department of Computer Science, Princeton University, Princeton, NJ, USA.
Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA.

Olli T Raitakari (OT)

Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland.
Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.

Mika Kähönen (M)

Department of Clinical Physiology, Tampere University Hospital, and Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland.

Ozren Polašek (O)

Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.
University of Split School of Medicine, Split, Croatia.

Ulf Gyllensten (U)

Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala Universitet, Uppsala, Sweden.

Igor Rudan (I)

Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.

Ian J Deary (IJ)

Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
Department of Psychology, University of Edinburgh, Edinburgh, UK.

Nicole M Probst-Hensch (NM)

Swiss Tropical and Public Health Institute, Basel, Switzerland.
University of Basel, Basel, Switzerland.

Holger Schulz (H)

Institute of Epidemiology, Helmholtz Zentrum Muenchen-German Research Center for Environmental Health, Neuherberg, Germany.
Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research (DZL), Munich, Germany.

Alan L James (AL)

Busselton Population Medical Research Institute, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.
Department of Pulmonary Physiology and Sleep Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.
School of Medicine and Pharmacology, The University of Western Australia, Crawley, Western Australia, Australia.

James F Wilson (JF)

Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.
Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.

Beate Stubbe (B)

Department of Internal Medicine B - Cardiology, Intensive Care, Pulmonary Medicine and Infectious Diseases, University Medicine Greifswald, Greifswald, Germany.

Eleftheria Zeggini (E)

Wellcome Sanger Institute, Hinxton, UK.
Institute of Translational Genomics, Helmholtz Zentrum Muenchen - German Research Center for Environmental Health, Neuherberg, Germany.

Marjo-Riitta Jarvelin (MR)

Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment & Health, School of Public Health, Imperial College London, London, UK.
Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland.
Biocenter Oulu, University of Oulu, Oulu, Finland.
Unit of Primary Health Care, Oulu University Hospital, Oulu, Finland.
Department of Life Sciences, College of Health and Life Sciences, Brunel University London, Uxbridge, UK.

Nick Wareham (N)

MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, UK.

Edwin K Silverman (EK)

Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA.

Caroline Hayward (C)

Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.

Andrew P Morris (AP)

Department of Biostatistics, University of Liverpool, Liverpool, UK.
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.

Adam S Butterworth (AS)

MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
NIHR Blood and Transplant Research Unit in Donor Health and Genomics, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.

Robert A Scott (RA)

Target Sciences - R&D, GSK Medicines Research Centre, Stevenage, UK.

Robin G Walters (RG)

Nuffield Department of Population Health, University of Oxford, Oxford, UK.

Deborah A Meyers (DA)

Division of Genetics, Genomics and Precision Medicine, Department of Medicine, University of Arizona, Tucson, AZ, USA.

Michael H Cho (MH)

Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA.

David P Strachan (DP)

Population Health Research Institute, St George's, University of London, London, UK.

Ian P Hall (IP)

Division of Respiratory Medicine and NIHR-Nottingham Biomedical Research Centre, University of Nottingham, Nottingham, UK.

Martin D Tobin (MD)

Department of Health Sciences, University of Leicester, Leicester, UK. mt47@leicester.ac.uk.
National Institute for Health Research, Leicester Respiratory Biomedical Research Centre, Glenfield Hospital, Leicester, UK. mt47@leicester.ac.uk.

Louise V Wain (LV)

Department of Health Sciences, University of Leicester, Leicester, UK. lvw1@leicester.ac.uk.
National Institute for Health Research, Leicester Respiratory Biomedical Research Centre, Glenfield Hospital, Leicester, UK. lvw1@leicester.ac.uk.

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