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Updated: Jul 17, 2025

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
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MAP3K19 regulatory variation in populations with African ancestry may increase COVID-19 severity
Zhongshan Cheng1, Yi Cai2, Ke Zhang3
1Center for Applied Bioinformatics, St Jude Children's Research Hospital, 262 Danny Thomas Pl, Memphis, TN 38105, USA.
Abstract:
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 MAP3K19. MAP3K19 expression is induced during ciliogenesis and most abundant in ciliated tissues including lungs. Single-cell RNA sequencing analyses revealed that MAP3K19 is highly expressed in multiple ciliated cell types. As rs16831827∗T is associated with reduced MAP3K19 expression, it may increase the risk of severe COVID-19 by reducing MAP3K19 expression.
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