Trans-ethnic genome-wide association study of severe COVID-19

Abstract

COVID-19 has caused numerous infections with diverse clinical symptoms. To identify human genetic variants contributing to the clinical development of COVID-19, we genotyped 1457 (598/859 with severe/mild symptoms) and sequenced 1141 (severe/mild: 474/667) patients of Chinese ancestry. We further incorporated 1401 genotyped and 948 sequenced ancestry-matched population controls, and tested genome-wide association on 1072 severe cases versus 3875 mild or population controls, followed by trans-ethnic meta-analysis with summary statistics of 3199 hospitalized cases and 897,488 population controls from the COVID-19 Host Genetics Initiative. We identified three significant signals outside the well-established 3p21.31 locus: an intronic variant in FOXP4-AS1 (rs1853837, odds ratio OR\u2009=\u20091.28, P\u2009=\u20092.51\u2009×\u200910−10, allele frequencies in Chinese/European AF\u2009=\u20090.345/0.105), a frameshift insertion in ABO (rs8176719, OR\u2009=\u20091.19, P\u2009=\u20098.98\u2009×\u200910−9, AF\u2009=\u20090.422/0.395) and a Chinese-specific intronic variant in MEF2B (rs74490654, OR\u2009=\u20098.73, P\u2009=\u20091.22\u2009×\u200910−8, AF\u2009=\u20090.004/0). These findings highlight an important role of the adaptive immunity and the ABO blood-group system in protection from developing severe COVID-19.