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

Issued Date

2019-03-01

Resource Type

Article

ISSN

15461718
10614036

DOI

10.1038/s41588-018-0321-7

Other identifier(s)

2-s2.0-85062074587

Rights

Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

Nature Genetics. Vol.51, No.3 (2019), 481-493

Suggested Citation

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 New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries. Nature Genetics. Vol.51, No.3 (2019), 481-493. doi:10.1038/s41588-018-0321-7 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/50248

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Thesis

Title

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

Author(s)

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

Other Contributor(s)

VA Boston Healthcare System
 Simons Foundation
 Centro de Investigación Biomédica En Red de Salud Mental
 National Institute for Health and Welfare
 National Jewish Health
 Wellcome Trust Centre for Human Genetics
 GlaxoSmithKline, USA
 Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval
 University of Leicester
 Université Laval
 University of Western Australia
 University of Cambridge
 Universitetet i Bergen
 Ludwig-Maximilians-Universität München
 University of Colorado at Denver Anschutz Medical Campus
 Walter and Eliza Hall Institute of Medical Research
 University of Edinburgh
 University of Oxford
 University of Melbourne
 Sir Charles Gairdner Hospital
 Turun Yliopistollinen Keskussairaala
 School of Clinical Medicine
 Helmholtz Center Munich German Research Center for Environmental Health
 University of California, San Francisco
 University of Dundee College of Medicine, Dentistry and Nursing
 Universitat Basel
 Swiss Tropical and Public Health Institute (Swiss TPH)
 Universitat Autònoma de Barcelona
 St Mary's Hospital London
 University of Liverpool
 GlaxoSmithKline plc.
 Brunel University London
 Addenbrooke's Hospital
 Brigham and Women's Hospital
 Oulu University Hospital
 Imperial College London
 University of Nottingham
 Icahn School of Medicine at Mount Sinai
 Oulun Yliopisto
 Edinburgh Medical School, Medical Research Council Human Genetics Unit
 Hospital Universitari Vall d'Hebron
 Faculty of Medicine, Siriraj Hospital, Mahidol University
 Tampereen Yliopisto
 University of Aberdeen School of Medicine
 The University of British Columbia
 University of Arizona
 University of Western Australia Faculty of Medicine and Dentistry
 University Hospital of Tampere
 Merck & Co., Inc.
 Sveučilište u Splitu
 Turun yliopisto
 Boston University School of Medicine
 Johns Hopkins Bloomberg School of Public Health
 University of Groningen, University Medical Center Groningen
 Wellcome Sanger Institute
 Peking University Health Science Center
 Uppsala Universitet
 Princeton University
 Helsingin Yliopisto
 Westfälische Wilhelms-Universität Münster
 Gossamer Bio
 Member of the German Center for Lung Research (DZL)
 University Medicine Greifswald

Abstract

© 2019, The Author(s), under exclusive licence to Springer Nature America, Inc. 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.

Keyword(s)

Biochemistry, Genetics and Molecular Biology

Availability

URI

https://repository.li.mahidol.ac.th/handle/20.500.14594/50248

Collections

Scopus 2019