A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Genetic Associations and Architecture of Asthma-COPD Overlap
Tekijät: 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
Kustantaja: Elsevier Inc.
Julkaisuvuosi: 2022
Journal: Chest
Tietokannassa oleva lehden nimi: Chest
Vuosikerta: 161
Numero: 5
Aloitussivu: 1155
Lopetussivu: 1166
eISSN: 0012-3692
DOI: https://doi.org/10.1016/j.chest.2021.12.674
Verkko-osoite: https://doi.org/10.1016/j.chest.2021.12.674
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/175156361
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.
Ladattava julkaisu This is an electronic reprint of the original article. |  |
