Expanded COVID-19 phenotype definitions reveal distinct patterns of genetic association and protective effects

• Main Authors: AncestryDNA Science Team (Author), Ball, C.A (Author), Berkowitz, N. (Author), Coignet, M.V (Author), Gaddis, M. (Author), Girshick, A.R (Author), Guturu, H. (Author), Haug Baltzell, A.K (Author), Hong, E.L (Author), Knight, S.C (Author), McCurdy, S.R (Author), Park, D.S (Author), Partha, R. (Author), Pavlovic, M. (Author), Rand, K.A (Author), Rhead, B. (Author), Roberts, G.H.L (Author), Ruiz, L. (Author), Sass, C. (Author), Turrisini, D.A (Author), Zhang, M. (Author)
• Format: Article
• Language: English
• Published: NLM (Medline) 2022
• Online Access: View Fulltext in Publisher

 Multiple COVID-19 genome-wide association studies (GWASs) have identified reproducible genetic associations indicating that there is a genetic component to susceptibility and severity risk. To complement these studies, we collected deep coronavirus disease 2019 (COVID-19) phenotype data from a survey of 736,723 AncestryDNA research participants. With these data, we defined eight phenotypes related to COVID-19 outcomes: four phenotypes that align with previously studied COVID-19 definitions and four 'expanded' phenotypes that focus on susceptibility given exposure, mild clinical manifestations and an aggregate score of symptom severity. We performed a replication analysis of 12 previously reported COVID-19 genetic associations with all eight phenotypes in a trans-ancestry meta-analysis of AncestryDNA research participants. In this analysis, we show distinct patterns of association at the 12 loci with the eight outcomes that we assessed. We also performed a genome-wide discovery analysis of all eight phenotypes, which did not yield new genome-wide significant loci but did suggest that three of the four 'expanded' COVID-19 phenotypes have enhanced power to capture protective genetic associations relative to the previously studied phenotypes. Thus, we conclude that continued large-scale ascertainment of deep COVID-19 phenotype data would likely represent a boon for COVID-19 therapeutic target identification. © 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.