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. 2021 Sep 7:8:738687.
doi: 10.3389/fmed.2021.738687. eCollection 2021.

Unraveling Risk Genes of COVID-19 by Multi-Omics Integrative Analyses

Ancha Baranova  1   2 , Hongbao Cao  1 , Fuquan Zhang  3   4
Affiliations

Unraveling Risk Genes of COVID-19 by Multi-Omics Integrative Analyses

Ancha Baranova et al. Front Med (Lausanne). .

Abstract

Objectives: Uncovering the genetic basis of COVID-19 may shed insight into its pathogenesis and help to improve treatment measures. We aimed to investigate the host genetic variants associated with COVID-19. Methods: The summary result of a COVID-19 GWAS (9,373 hospitalized COVID-19 cases and 1,197,256 controls) was obtained from the COVID-19 Host Genetic Initiative GWAS meta-analyses. We tested colocalization of the GWAS signals of COVID-19 with expression and methylation quantitative traits loci (eQTL and mQTL, respectively) using the summary data-based Mendelian randomization (SMR) analysis. Four eQTL and two mQTL datasets were utilized in the SMR analysis, including CAGE blood eQTL data (n = 2,765), GTEx v7 blood (n = 338) and lung (n = 278) eQTL data, Geuvadis lymphoblastoid cells eQTL data, LBC-BSGS blood mQTL data (n = 1,980), and Hannon blood mQTL summary data (n = 1,175). We conducted a transcriptome-wide association study (TWAS) on COVID-19 with precomputed prediction models of GTEx v8 eQTL in lung and blood using S-PrediXcan. Results: Our SMR analyses identified seven protein-coding genes (TYK2, IFNAR2, OAS1, OAS3, XCR1, CCR5, and MAPT) associated with COVID-19, including two novel risk genes, CCR5 and tau-encoding MAPT. The TWAS revealed four genes for COVID-19 (CXCR6, CCR5, CCR9, and PIGN), including two novel risk genes, CCR5 and PIGN. Conclusion: Our study highlighted the functional relevance of some known genome-wide risk genes of COVID-19 and revealed novel genes contributing to differential outcomes of COVID-19 disease.

Keywords: COVID-19; GWAS; TWAS; eQTL; mQTL.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Summary data-based Mendelian randomization (SMR) analysis of COVID-19. Each horizontal dashed line denotes a genome-wide significance level adjusted by Bonferroni.
Figure 2
Figure 2
Two loci from the SMR analysis. (A): Top plot, gray dots represent the P-values for SNPs from the COVID-19 GWAS. Bottom plots, the mQTL P-values of SNPs from the Hannon study for the cg14546840 and cg17786516 probes tagging CCR5 and CCR5AS, respectively. Highlighted in red are the genes (CCR5 and CCR5AS) that passed the SMR and HEIDI tests. (B): Top plot, gray dots represent the P-values for SNPs from the COVID-19 GWAS. The bottom plot, the mQTL P-values of SNPs from the LBC-BSGS study for the cg02228913 probe tagging MAPT. Highlighted in red is the gene (MAPT) that passed the SMR and HEIDI tests.
See this image and copyright information in PMC

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