Genetic associations and architecture of asthma-chronic obstructive pulmonary disease overlap.
Authors
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
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
Publication Date
2022-01-29Journal Title
Chest
ISSN
0012-3692
Publisher
Elsevier BV
Type
Article
This Version
AM
Physical Medium
Print-Electronic
Metadata
Show full item recordCitation
John, C., Guyatt, A. L., Shrine, N., Packer, R., Olafsdottir, T. A., Liu, J., Hayden, L. P., et al. (2022). Genetic associations and architecture of asthma-chronic obstructive pulmonary disease overlap.. Chest https://doi.org/10.1016/j.chest.2021.12.674
Abstract
BACKGROUND: Some individuals have characteristics of both asthma and chronic obstructive pulmonary disease (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 cases and 40,360 controls without asthma or COPD of European ancestry in UK Biobank (Stage 1). We followed up promising signals which had p<5×10-6, and that remained associated in analyses comparing: i) asthma-COPD overlap vs asthma-only controls, and ii) asthma-COPD overlap versus COPD-only controls). These variants were analysed in 12 independent cohorts (Stage 2). RESULTS: We selected 31 independent variants for further investigation in stage 2, and discovered eight novel signals (P<5x10-8) 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.
Keywords
asthma, chronic obstructive pulmonary disease, epidemiology, genome-wide association study, spirometry
Sponsorship
MRC (MC_UU_00006/1)
Identifiers
External DOI: https://doi.org/10.1016/j.chest.2021.12.674
This record's URL: https://www.repository.cam.ac.uk/handle/1810/333667
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