Catherine John
Genetic Associations and Architecture of Asthma-COPD Overlap
John, Catherine; Guyatt, Anna L.; Shrine, Nick; Packer, Richard; Olafsdottir, Thorunn A.; Liu, Jiangyuan; Hayden, Lystra P.; Chu, Su H.; Koskela, Jukka T.; Luan, Jian’an; Li, Xingnan; Terzikhan, Natalie; Xu, Hanfei; Bartz, Traci M.; Petersen, Hans; Leng, Shuguang; Belinsky, Steven A.; Cepelis, Aivaras; Hernández Cordero, Ana I.; Obeidat, Ma’en; Thorleifsson, Gudmar; Meyers, Deborah A.; Bleecker, Eugene R.; Sakoda, Lori C.; Iribarren, Carlos; Tesfaigzi, Yohannes; Gharib, Sina A.; Dupuis, Josée; Brusselle, Guy; Lahousse, Lies; Ortega, Victor E.; Jonsdottir, Ingileif; Sin, Don D.; Bossé, Yohan; van den Berge, Maarten; Nickle, David; Quint, Jennifer K.; Sayers, Ian; Hall, Ian P.; Langenberg, Claudia; Ripatti, Samuli; Laitinen, Tarja; Wu, Ann C.; Lasky-Su, Jessica; Bakke, Per; Gulsvik, Amund; Hersh, Craig P.; Hayward, Caroline; Langhammer, Arnulf; Brumpton, Ben; Stefansson, Kari; Cho, Michael H.; Wain, Louise V.; Tobin, Martin D.
Authors
Anna L. Guyatt
Nick Shrine
Richard Packer
Thorunn A. Olafsdottir
Jiangyuan Liu
Lystra P. Hayden
Su H. Chu
Jukka T. Koskela
Jian’an Luan
Xingnan Li
Natalie Terzikhan
Hanfei Xu
Traci M. Bartz
Hans Petersen
Shuguang Leng
Steven A. Belinsky
Aivaras Cepelis
Ana I. Hernández Cordero
Ma’en Obeidat
Gudmar Thorleifsson
Deborah A. Meyers
Eugene R. Bleecker
Lori C. Sakoda
Carlos Iribarren
Yohannes Tesfaigzi
Sina A. Gharib
Josée Dupuis
Guy Brusselle
Lies Lahousse
Victor E. Ortega
Ingileif Jonsdottir
Don D. Sin
Yohan Bossé
Maarten van den Berge
David Nickle
Jennifer K. Quint
Professor IAN SAYERS ian.sayers@nottingham.ac.uk
Professor of Respiratory Molecular Genetics
IAN HALL IAN.HALL@NOTTINGHAM.AC.UK
Professor of Molecular Medicine
Claudia Langenberg
Samuli Ripatti
Tarja Laitinen
Ann C. Wu
Jessica Lasky-Su
Per Bakke
Amund Gulsvik
Craig P. Hersh
Caroline Hayward
Arnulf Langhammer
Ben Brumpton
Kari Stefansson
Michael H. Cho
Louise V. Wain
Martin D. Tobin
Abstract
Background
Some people have characteristics of both asthma and COPD (asthma-COPD overlap), and evidence suggests they experience worse outcomes than those with either condition alone.
Research Question
What is the genetic architecture of asthma-COPD overlap, and do the determinants of risk for asthma-COPD overlap differ from those for COPD or asthma?
Study Design and Methods
We conducted a genome-wide association study in 8,068 asthma-COPD overlap case subjects and 40,360 control subjects without asthma or COPD of European ancestry in UK Biobank (stage 1). We followed up promising signals (P < 5 × 10–6) that remained associated in analyses comparing (1) asthma-COPD overlap vs asthma-only control subjects, and (2) asthma-COPD overlap vs COPD-only control subjects. These variants were analyzed in 12 independent cohorts (stage 2).
Results
We selected 31 independent variants for further investigation in stage 2, and discovered eight novel signals (P < 5 × 10–8) for asthma-COPD overlap (meta-analysis of stage 1 and 2 studies). These signals suggest a spectrum of shared genetic influences, some predominantly influencing asthma (FAM105A, GLB1, PHB, TSLP), others predominantly influencing fixed airflow obstruction (IL17RD, C5orf56, HLA-DQB1). One intergenic signal on chromosome 5 had not been previously associated with asthma, COPD, or lung function. Subgroup analyses suggested that associations at these eight signals were not driven by smoking or age at asthma diagnosis, and in phenome-wide scans, eosinophil counts, atopy, and asthma traits were prominent.
Interpretation
We identified eight signals for asthma-COPD overlap, which may represent loci that predispose to type 2 inflammation, and serious long-term consequences of asthma.
Citation
John, C., Guyatt, A. L., Shrine, N., Packer, R., Olafsdottir, T. A., Liu, J., …Tobin, M. D. (2022). Genetic Associations and Architecture of Asthma-COPD Overlap. Chest, 161(5), 1155-1166. https://doi.org/10.1016/j.chest.2021.12.674
Journal Article Type | Article |
---|---|
Acceptance Date | Jan 1, 2022 |
Online Publication Date | Jan 28, 2022 |
Publication Date | 2022-05 |
Deposit Date | Mar 14, 2024 |
Publicly Available Date | Mar 15, 2024 |
Journal | Chest |
Print ISSN | 0012-3692 |
Publisher | Elsevier |
Peer Reviewed | Peer Reviewed |
Volume | 161 |
Issue | 5 |
Pages | 1155-1166 |
DOI | https://doi.org/10.1016/j.chest.2021.12.674 |
Public URL | https://nottingham-repository.worktribe.com/output/23529235 |
Files
PIIS0012369222001982
(674 Kb)
PDF
Publisher Licence URL
https://creativecommons.org/licenses/by/4.0/
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