Genetic Associations and Architecture of Asthma-COPD Overlap
Quint Jennifer K; Sin Don D; Packer Richard; Lasky-Su Jessica; Terzikhan Natalie; Bleecker Eugene R; Liu Jiangyuan; Ortega Victor E; John Catherine; Thorleifsson Gudmar; Meyers Deborah A; Luan Jian'an; Nickle David; Stefansson Kari; Hayward Caroline; Chu Su H; Bakke Per; Petersen Hans; Langhammer Arnulf; Jonsdottir Ingileif; Shrine Nick; Sayers Ian; Guyatt Anna L; Wain Louise V; Obeidat Ma'en; Wu Ann C; Ripatti Samuli; Bossé Yohan; Hayden Lystra P; Tobin Martin D; Koskela Jukka T; Xu Hanfei; Bartz Traci M; Hernández Cordero Ana I; Leng Shuguang; Li Xingnan; Cho Michael H; Gharib Sina A; Tesfaigzi Yohannes; Cepelis Aivaras; Laitinen Tarja; Sakoda Lori C; Dupuis Josée; Brusselle Guy; van den Berge Maarten; Olafsdottir Thorunn A; Hall Ian P; Brumpton Ben; Iribarren Carlos; Lahousse Lies; Langenberg Claudia; Belinsky Steven A; Hersh Craig P; Gulsvik Amund
https://urn.fi/URN:NBN:fi-fe2022081154169
Tiivistelmä
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.
Kokoelmat
- Rinnakkaistallenteet [19207]