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. 2021 Apr 23;24(4):102322.
doi: 10.1016/j.isci.2021.102322. Epub 2021 Mar 17.

Common variants at 21q22.3 locus influence MX1 and TMPRSS2 gene expression and susceptibility to severe COVID-19

Immacolata Andolfo  1   2 , Roberta Russo  1   2 , Vito Alessandro Lasorsa  1   2 , Sueva Cantalupo  1   2 , Barbara Eleni Rosato  1   2 , Ferdinando Bonfiglio  3 , Giulia Frisso  1   2 , Pasquale Abete  4 , Gian Marco Cassese  4 , Giuseppe Servillo  5 , Gabriella Esposito  1   2 , Ivan Gentile  6 , Carmelo Piscopo  7 , Romolo Villani  8 , Giuseppe Fiorentino  9 , Pellegrino Cerino  10 , Carlo Buonerba  10 , Biancamaria Pierri  10   11 , Massimo Zollo  1   2 , Achille Iolascon  1   2 , Mario Capasso  1   2
Affiliations

Common variants at 21q22.3 locus influence MX1 and TMPRSS2 gene expression and susceptibility to severe COVID-19

Immacolata Andolfo et al. iScience. .

Abstract

The established risk factors of coronavirus disease 2019 (COVID-19) are advanced age, male sex, and comorbidities, but they do not fully explain the wide spectrum of disease manifestations. Genetic factors implicated in the host antiviral response provide for novel insights into its pathogenesis. We performed an in-depth genetic analysis of chromosome 21 exploiting the genome-wide association study data, including 6,406 individuals hospitalized for COVID-19 and 902,088 controls with European genetic ancestry from the COVID-19 Host Genetics Initiative. We found that five single nucleotide polymorphisms within TMPRSS2 and near MX1 gene show associations with severe COVID-19. The minor alleles of the five single nucleotide polymorphisms (SNPs) correlated with a reduced risk of developing severe COVID-19 and high level of MX1 expression in blood. Our findings demonstrate that host genetic factors can influence the different clinical presentations of COVID-19 and that MX1 could be a potential therapeutic target.

Keywords: Genetics; Genomics.

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Conflict of interest statement

The authors declare that there are no competing interests.

Figures

None
Graphical abstract
Figure 1
Figure 1
Regional association plots of the SNPs at three independent association signals of chromosome 21 Plots were generated using LocusZoom. Y axes represent the significance of association (−log10 transformed p values) and the recombination rate. SNPs are color-coded based on pairwise linkage disequilibrium (r2) with indicated lead SNPs: rs13050728 (A), rs111783124 (B) and rs3787946 (C).
Figure 2
Figure 2
Enrichment of SNPs in regulatory regions and eQTL analyses The statistically significant fold enrichments (p < 0.05 after Bonferroni correction) of SNPs in regulatory DNA regions active in different tissues are shown (A). eQTL violin plots between genotypes of rs3787946 (B) and rs3787946 (C) with MX1 and TMPRSS2 expression from the Genotype-Tissue Expression (GTEx). The significance threshold adjusted for multiple comparisons is equal to 0.000055.
See this image and copyright information in PMC

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