TY - JOUR T1 - A genome-wide association study of asthma-COPD overlap syndrome (ACOS) JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.congress-2020.4919 VL - 56 IS - suppl 64 SP - 4919 AU - Catherine John AU - Anna L Guyatt AU - Nick Shrine AU - Thorunn Olafsdottir AU - Jiangyuan Liu AU - Lystra Hayden AU - Su H Chu AU - Jukka Koskela AU - Jian'An Luan AU - Xingnan Li AU - Natalie Terzikhan AU - Hanfei Xu AU - Traci M Bartz AU - Hans Petersen AU - Shuguang Leng AU - Gudmar Thorleifsson AU - Deborah A Meyers AU - Eugene R Bleecker AU - Lori C Sakoda AU - Carlos Iribarren AU - Yohannes Tesfaigzi AU - Sina A Gharib AU - Josee Dupuis AU - Lies Lahousse AU - Victor E Ortega AU - Kari Stefansson AU - Ian Sayers AU - Ian P Hall AU - Claudia Langenberg AU - Samuli Ripatti AU - Tarja Laitinen AU - Ann C Wu AU - Jessica Lasky-Su AU - Caroline Hayward AU - Ben Brumpton AU - Arnulf Langhammer AU - Ingileif Jonsdottir AU - Michael H Cho AU - Louise V Wain AU - Martin D Tobin Y1 - 2020/09/07 UR - http://erj.ersjournals.com/content/56/suppl_64/4919.abstract N2 - Individuals with characteristics of both asthma and COPD (asthma-COPD overlap syndrome, ACOS) experience significantly worse outcomes than those with asthma or COPD alone. Despite hundreds of genetic associations with asthma, COPD and lung function, no genetic variants have specifically been associated with ACOS. We hypothesized that there are genetic determinants of ACOS and sought to identify these in a genome-wide association study.We defined ACOS based on self-reported doctor-diagnosed asthma and spirometric GOLD2+ airflow limitation. We tested 7693381 genetic variants for association with ACOS in 8068 cases and 40360 healthy controls from UK Biobank (stage 1). We identified signals where P<5x10-6 in this analysis, and where P<0.01 in two sensitivity analyses in UK Biobank using (i) controls with asthma but no COPD and (ii) controls with COPD but no asthma. For these signals, we undertook a meta-analysis of the UK Biobank results and results from fifteen independent cohorts with an additional 4301 cases and 48609 controls (stage 2). All cases and controls were of European ancestry.Thirty-one genetic variants met criteria for inclusion in stage 2. Of these, eight were associated at genome-wide significance (P<5x10-8) and showed stronger evidence of association in the stage 2 meta-analysis than in UK Biobank alone, including signals near HLA-DQB1, C5orf56, GLB1, FAM105A, PHB, TSLP and IL17RD, and an intergenic signal on chromosome 5 not previously associated with asthma, COPD or lung function.Whilst our results suggest that many genetic variants associated with ACOS are shared with asthma and/or COPD, we identify a new, distinct signal that may implicate cellular pathways characteristic of ACOS.FootnotesCite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 4919.This abstract was presented at the 2020 ERS International Congress, in session “Respiratory viruses in the "pre COVID-19" era”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only). ER -