MAP3K19 regulatory variation in populations with African ancestry may increase COVID-19 severity

To identify ancestry-linked genetic risk variants associated with COVID-19 hospitalization, we performed an integrative analysis of two genome-wide association studies and resolved four single nucleotide polymorphisms more frequent in COVID-19-hospitalized patients with non-European ancestry. Among them, the COVID-19 risk SNP rs16831827 shows the largest difference in minor allele frequency (MAF) between populations with African and European ancestry and also shows higher MAF in hospitalized COVID-19 patients among cohorts of mixed ancestry (odds ratio [OR] = 1.20, 95% CI: 1.10-1.30) and entirely African ancestry (OR = 1.30, 95% CI: 1.02-1.67). rs16831827 is an expression quantitative trait locus of . expression is induced during ciliogenesis and most abundant in ciliated tissues including lungs. Single-cell RNA sequencing analyses revealed that is highly expressed in multiple ciliated cell types. As rs16831827∗T is associated with reduced expression, it may increase the risk of severe COVID-19 by reducing expression.