Genetic associations and architecture of asthma-chronic obstructive pulmonary disease overlap
Anna L Guyatt,
Thorunn A Olafsdottir,
Lystra P. Hayden,
Su H Chu,
Jukka T. Koskela,
Traci M Bartz,
Scott A Belinsky,
Ana I Hernandez Cordero,
Deborah A Meyer,
Eugene R Bleecker,
Lori C. Sakoda,
Sina A Gharib,
Victor E Ortega,
Don D. Sin,
Maarten van den Berge,
Jennifer K Quint,
Ian P Hall,
Ann C Wu,
Craig P. Hersh,
Louise V Wain,
Martin D Tobin
Posted 30 Nov 2020
medRxiv DOI: 10.1101/2020.11.26.20236760
Posted 30 Nov 2020
Some individuals have characteristics of both asthma and COPD (asthma-COPD overlap, ACO), and evidence suggests they experience worse outcomes than those with either condition alone. Improved knowledge of the genetic architecture would contribute to understanding whether determinants of risk in this group differ from those in COPD or asthma. We conducted a genome-wide association study in 8,068 cases and 40,360 controls of European ancestry from UK Biobank (stage 1). After excluding variants only associated with asthma or COPD we selected 31 variants for further investigation in 12 additional cohorts (stage 2), and discovered eight novel signals for ACO in a meta-analysis of stage 1 and 2 studies. Our signals include an intergenic signal on chromosome 5 not previously associated with asthma, COPD or lung function, and suggest a spectrum of shared and distinct genetic influences in asthma, COPD and ACO. A number of signals may represent loci that predispose to serious long-term consequences in people with asthma.
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