Publication:
Chronic obstructive pulmonary disease and related phenotypes: polygenic risk scores in population-based and case-control cohorts

Issued Date

2020-07-01

Resource Type

Article

ISSN

22132619
22132600

DOI

10.1016/S2213-2600(20)30101-6

Other identifier(s)

2-s2.0-85087427951

Rights

Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

The Lancet Respiratory Medicine. Vol.8, No.7 (2020), 696-708

Suggested Citation

Matthew Moll, Phuwanat Sakornsakolpat, Nick Shrine, Brian D. Hobbs, Dawn L. DeMeo, Catherine John, Anna L. Guyatt, Michael J. McGeachie, Sina A. Gharib, Ma'en Obeidat, Lies Lahousse, Sara R.A. Wijnant, Guy Brusselle, Deborah A. Meyers, Eugene R. Bleecker, Xingnan Li, Ruth Tal-Singer, Ani Manichaikul, Stephen S. Rich, Sungho Won, Woo Jin Kim, Ah Ra Do, George R. Washko, R. Graham Barr, Bruce M. Psaty, Traci M. Bartz, Nadia N. Hansel, Kathleen Barnes, John E. Hokanson, James D. Crapo, David Lynch, Per Bakke, Amund Gulsvik, Ian P. Hall, Louise Wain, María Soler Artigas, Victoria E. Jackson, David P. Strachan, Jennie Hui, Alan L. James, Shona M. Kerr, Ozren Polasek, Veronique Vitart, Jonathan Marten, Igor Rudan, Mika Kähönen, Ida Surakka, Christian Gieger, Stefan Karrasch, Rajesh Rawal, Holger Schulz, Ian J. Deary, Sarah E. Harris, Stefan Enroth, Ulf Gyllensten, Medea Imboden, Nicole M. Probst-Hensch, Terho Lehtimäki, Olli T. Raitakari, Claudia Langenberg, Jian'an Luan, Nick Wareham, Jing Hua Zhao, Caroline Hayward, Alison Murray, David J. Porteous, Blair H. Smith, Marjo Riitta Jarvelin, Matthias Wielscher, Peter K. Joshi, Katherine A. Kentistou, Paul RHJ Timmers, James F. Wilson, James P. Cook, Lars Lind, Anubha Mahajan, Andrew P. Morris, Ralf Ewert, Georg Homuth, Beate Stubbe, Stefan Weiss, Eleftheria Zeggini, Scott T. Weiss, Edwin K. Silverman, Frank Dudbridge, Martin D. Tobin, Michael H. Cho Chronic obstructive pulmonary disease and related phenotypes: polygenic risk scores in population-based and case-control cohorts. The Lancet Respiratory Medicine. Vol.8, No.7 (2020), 696-708. doi:10.1016/S2213-2600(20)30101-6 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/58118

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Title

Chronic obstructive pulmonary disease and related phenotypes: polygenic risk scores in population-based and case-control cohorts

Author(s)

Matthew Moll
 Phuwanat Sakornsakolpat
 Nick Shrine
 Brian D. Hobbs
 Dawn L. DeMeo
 Catherine John
 Anna L. Guyatt
 Michael J. McGeachie
 Sina A. Gharib
 Ma'en Obeidat
 Lies Lahousse
 Sara R.A. Wijnant
 Guy Brusselle
 Deborah A. Meyers
 Eugene R. Bleecker
 Xingnan Li
 Ruth Tal-Singer
 Ani Manichaikul
 Stephen S. Rich
 Sungho Won
 Woo Jin Kim
 Ah Ra Do
 George R. Washko
 R. Graham Barr
 Bruce M. Psaty
 Traci M. Bartz
 Nadia N. Hansel
 Kathleen Barnes
 John E. Hokanson
 James D. Crapo
 David Lynch
 Per Bakke
 Amund Gulsvik
 Ian P. Hall
 Louise Wain
 María Soler Artigas
 Victoria E. Jackson
 David P. Strachan
 Jennie Hui
 Alan L. James
 Shona M. Kerr
 Ozren Polasek
 Veronique Vitart
 Jonathan Marten
 Igor Rudan
 Mika Kähönen
 Ida Surakka
 Christian Gieger
 Stefan Karrasch
 Rajesh Rawal
 Holger Schulz
 Ian J. Deary
 Sarah E. Harris
 Stefan Enroth
 Ulf Gyllensten
 Medea Imboden
 Nicole M. Probst-Hensch
 Terho Lehtimäki
 Olli T. Raitakari
 Claudia Langenberg
 Jian'an Luan
 Nick Wareham
 Jing Hua Zhao
 Caroline Hayward
 Alison Murray
 David J. Porteous
 Blair H. Smith
 Marjo Riitta Jarvelin
 Matthias Wielscher
 Peter K. Joshi
 Katherine A. Kentistou
 Paul RHJ Timmers
 James F. Wilson
 James P. Cook
 Lars Lind
 Anubha Mahajan
 Andrew P. Morris
 Ralf Ewert
 Georg Homuth
 Beate Stubbe
 Stefan Weiss
 Eleftheria Zeggini
 Scott T. Weiss
 Edwin K. Silverman
 Frank Dudbridge
 Martin D. Tobin
 Michael H. Cho

Other Contributor(s)

National Jewish Health
 GlaxoSmithKline, USA
 University Hospital of Ghent
 Universiteit Gent
 University of Leicester
 Erasmus MC
 University of Virginia School of Medicine
 Queen's Medical Centre
 Universitetet i Bergen
 University of Washington School of Medicine
 University of Colorado at Denver Anschutz Medical Campus
 Columbia University Irving Medical Center
 University of Virginia
 Kaiser Permanente
 Brigham and Women's Hospital
 University of Washington, Seattle
 Seoul National University
 Faculty of Medicine, Siriraj Hospital, Mahidol University
 The University of British Columbia
 University of Colorado at Denver
 The University of Arizona
 Glenfield Hospital
 Johns Hopkins University
 Harvard Medical School
 Kangwon National University

Abstract

© 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Background: Genetic factors influence chronic obstructive pulmonary disease (COPD) risk, but the individual variants that have been identified have small effects. We hypothesised that a polygenic risk score using additional variants would predict COPD and associated phenotypes. Methods: We constructed a polygenic risk score using a genome-wide association study of lung function (FEV1 and FEV1/forced vital capacity [FVC]) from the UK Biobank and SpiroMeta. We tested this polygenic risk score in nine cohorts of multiple ethnicities for an association with moderate-to-severe COPD (defined as FEV1/FVC <0·7 and FEV1 <80% of predicted). Associations were tested using logistic regression models, adjusting for age, sex, height, smoking pack-years, and principal components of genetic ancestry. We assessed predictive performance of models by area under the curve. In a subset of studies, we also studied quantitative and qualitative CT imaging phenotypes that reflect parenchymal and airway pathology, and patterns of reduced lung growth. Findings: The polygenic risk score was associated with COPD in European (odds ratio [OR] per SD 1·81 [95% CI 1·74–1·88] and non-European (1·42 [1·34–1·51]) populations. Compared with the first decile, the tenth decile of the polygenic risk score was associated with COPD, with an OR of 7·99 (6·56–9·72) in European ancestry and 4·83 (3·45–6·77) in non-European ancestry cohorts. The polygenic risk score was superior to previously described genetic risk scores and, when combined with clinical risk factors (ie, age, sex, and smoking pack-years), showed improved prediction for COPD compared with a model comprising clinical risk factors alone (AUC 0·80 [0·79–0·81] vs 0·76 [0·75–0·76]). The polygenic risk score was associated with CT imaging phenotypes, including wall area percent, quantitative and qualitative measures of emphysema, local histogram emphysema patterns, and destructive emphysema subtypes. The polygenic risk score was associated with a reduced lung growth pattern. Interpretation: A risk score comprised of genetic variants can identify a small subset of individuals at markedly increased risk for moderate-to-severe COPD, emphysema subtypes associated with cigarette smoking, and patterns of reduced lung growth. Funding: US National Institutes of Health, Wellcome Trust.

Keyword(s)

Medicine

Availability

URI

https://repository.li.mahidol.ac.th/handle/20.500.14594/58118

Collections

Scopus 2020