Publication:
Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations

Issued Date

2019-03-01

Resource Type

Article

ISSN

15461718
10614036

DOI

10.1038/s41588-018-0342-2

Other identifier(s)

2-s2.0-85062145797

Rights

Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

Nature Genetics. Vol.51, No.3 (2019), 494-505

Suggested Citation

Phuwanat Sakornsakolpat, Dmitry Prokopenko, Maxime Lamontagne, Nicola F. Reeve, Anna L. Guyatt, Victoria E. Jackson, Nick Shrine, Dandi Qiao, Traci M. Bartz, Deog Kyeom Kim, Mi Kyeong Lee, Jeanne C. Latourelle, Xingnan Li, Jarrett D. Morrow, Ma’en Obeidat, Annah B. Wyss, Per Bakke, R. Graham Barr, Terri H. Beaty, Steven A. Belinsky, Guy G. Brusselle, James D. Crapo, Kim de Jong, Dawn L. DeMeo, Tasha E. Fingerlin, Sina A. Gharib, Amund Gulsvik, Ian P. Hall, John E. Hokanson, Woo Jin Kim, David A. Lomas, Stephanie J. London, Deborah A. Meyers, George T. O’Connor, Stephen I. Rennard, David A. Schwartz, Pawel Sliwinski, David Sparrow, David P. Strachan, Ruth Tal-Singer, Yohannes Tesfaigzi, Jørgen Vestbo, Judith M. Vonk, Jae Joon Yim, Xiaobo Zhou, Yohan Bossé, Ani Manichaikul, Lies Lahousse, Edwin K. Silverman, H. Marike Boezen, Louise V. Wain, Martin D. Tobin, Brian D. Hobbs, Michael H. Cho, Chiara Batini, Jing Hua Zhao, Matthias Wielscher, Stefan Weiss, Katherine A. Kentistou, James P. Cook, Jennie Hui, Stefan Karrasch, Medea Imboden, Sarah E. Harris, Jonathan Marten, Stefan Enroth, Shona M. Kerr, Ida Surakka, Veronique Vitart, Terho Lehtimäki, Ralf Ewert, Christian Gieger, Georg Homuth, Peter K. Joshi, Claudia Langenberg, Lars Lind, Jian’an Luan, Anubha Mahajan, Alison Murray, David J. Porteous, Rajesh Rawal, Blair H. Smith, Paul R.H.J. Timmers, Olli T. Raitakari, Mika Kähönen, Ozren Polasek, 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, Caroline Hayward, Andrew P. Morris, Alvar Agusti Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations. Nature Genetics. Vol.51, No.3 (2019), 494-505. doi:10.1038/s41588-018-0342-2 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/50249

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Thesis

Title

Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations

Author(s)

Phuwanat Sakornsakolpat
 Dmitry Prokopenko
 Maxime Lamontagne
 Nicola F. Reeve
 Anna L. Guyatt
 Victoria E. Jackson
 Nick Shrine
 Dandi Qiao
 Traci M. Bartz
 Deog Kyeom Kim
 Mi Kyeong Lee
 Jeanne C. Latourelle
 Xingnan Li
 Jarrett D. Morrow
 Ma’en Obeidat
 Annah B. Wyss
 Per Bakke
 R. Graham Barr
 Terri H. Beaty
 Steven A. Belinsky
 Guy G. Brusselle
 James D. Crapo
 Kim de Jong
 Dawn L. DeMeo
 Tasha E. Fingerlin
 Sina A. Gharib
 Amund Gulsvik
 Ian P. Hall
 John E. Hokanson
 Woo Jin Kim
 David A. Lomas
 Stephanie J. London
 Deborah A. Meyers
 George T. O’Connor
 Stephen I. Rennard
 David A. Schwartz
 Pawel Sliwinski
 David Sparrow
 David P. Strachan
 Ruth Tal-Singer
 Yohannes Tesfaigzi
 Jørgen Vestbo
 Judith M. Vonk
 Jae Joon Yim
 Xiaobo Zhou
 Yohan Bossé
 Ani Manichaikul
 Lies Lahousse
 Edwin K. Silverman
 H. Marike Boezen
 Louise V. Wain
 Martin D. Tobin
 Brian D. Hobbs
 Michael H. Cho
 Chiara Batini
 Jing Hua Zhao
 Matthias Wielscher
 Stefan Weiss
 Katherine A. Kentistou
 James P. Cook
 Jennie Hui
 Stefan Karrasch
 Medea Imboden
 Sarah E. Harris
 Jonathan Marten
 Stefan Enroth
 Shona M. Kerr
 Ida Surakka
 Veronique Vitart
 Terho Lehtimäki
 Ralf Ewert
 Christian Gieger
 Georg Homuth
 Peter K. Joshi
 Claudia Langenberg
 Lars Lind
 Jian’an Luan
 Anubha Mahajan
 Alison Murray
 David J. Porteous
 Rajesh Rawal
 Blair H. Smith
 Paul R.H.J. Timmers
 Olli T. Raitakari
 Mika Kähönen
 Ozren Polasek
 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
 Caroline Hayward
 Andrew P. Morris
 Alvar Agusti

Other Contributor(s)

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
 National Institute of Tuberculosis and Lung Diseases, Warszawa
 University Hospital of Ghent
 Universiteit Gent
 University of Leicester
 Université Laval
 Erasmus MC
 University of Western Australia
 University of Cambridge
 Massachusetts General Hospital
 Universitetet i Bergen
 St George's University of London
 Ludwig-Maximilians-Universität München
 National Institute of Environmental Health Sciences
 University of Colorado at Denver Anschutz Medical Campus
 University of Edinburgh
 Sir Charles Gairdner Hospital
 Turun Yliopistollinen Keskussairaala
 School of Clinical Medicine
 Helmholtz Center Munich German Research Center for Environmental Health
 University of Dundee College of Medicine, Dentistry and Nursing
 Universitat Basel
 Swiss Tropical and Public Health Institute (Swiss TPH)
 Framingham Heart Study
 UCL
 University of Virginia
 University of Liverpool
 Brunel University London
 Brigham and Women's Hospital
 Oulu University Hospital
 University of Nebraska Medical Center
 University of Washington, Seattle
 Imperial College London
 University of Nottingham
 Oulun Yliopisto
 Edinburgh Medical School, Medical Research Council Human Genetics Unit
 Vagelos College of Physicians and Surgeons
 Faculty of Medicine, Siriraj Hospital, Mahidol University
 Tampereen Yliopisto
 University of Aberdeen School of Medicine
 Lovelace Respiratory Research Institute
 The University of British Columbia
 University of Arizona
 University of Colorado Health Sciences Center
 University of Western Australia Faculty of Medicine and Dentistry
 Glenfield Hospital
 University Hospital of Tampere
 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
 AstraZeneca
 Uppsala Universitet
 University of Manchester
 Helsingin Yliopisto
 Universitat de Barcelona
 Kangwon National University
 Seoul National University College of Medicine
 Westfälische Wilhelms-Universität Münster
 Member of the German Center for Lung Research (DZL)
 University Medicine Greifswald
 National Institute for Health Research Nottingham Biomedical Research Centre

Abstract

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

Keyword(s)

Biochemistry, Genetics and Molecular Biology

Availability

URI

https://repository.li.mahidol.ac.th/handle/20.500.14594/50249

Collections

Scopus 2019