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Integrative Genomics Analysis Reveals a 21q22.11 Locus Contributing Risk to COVID-19.

Abstract

The systematic identification of host genetic risk factors is essential for the understanding and treatment of COVID-19. By performing a meta-analysis of two independent genome-wide association summary datasets (N = 680 128), a novel locus at 21q22.11 was identified to be associated with COVID-19 infection (rs9976829 in IFNAR2-IL10RB, OR = 1.16, 95% CI = 1.09-1.23, P = 2.57 x 10-6). The rs9976829 represents a strong splicing quantitative trait locus for both IFNAR2 and IL10RB genes, especially in lung tissue (P = 1.8 x 10-24). Integrative genomics analysis of combining GWAS with eQTL data showed the expression variations of IFNAR2 and IL10RB have prominent effects on COVID-19 in various types of tissues, especially in lung tissue. The majority of IFNAR2-expressing cells were dendritic cells (40%) and plasmacytoid dendritic cells (38.5%), and IL10RB-expressing cells were mainly nonclassical monocytes (29.6%). IFNAR2 and IL10RB are targeted by several interferons-related drugs. Together, our results uncover 21q22.11 as a novel susceptibility locus for COVID-19, in which individuals with G alleles of rs9976829 have a higher probability of COVID-19 susceptibility than those with non-G alleles.

Authors: Ma Y, Huang Y, Zhao S, Yao Y, Zhang Y, Qu J, Wu N, Su J,
Journal: Hum Mol Genet; 2021Jun 17;30(13):1247-1258 . doi:10.1093/hmg/ddab125
Year: 2021
PubMed: PMID: 33949668 (Go to PubMed)