AUTHOR=Baranova Ancha , Cao Hongbao , Zhang Fuquan 

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

JOURNAL=Frontiers in Medicine

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2021.738687

DOI=10.3389/fmed.2021.738687

ISSN=2296-858X

ABSTRACT=<p><bold>Objectives:</bold> 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.</p><p><bold>Methods:</bold> 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 (<italic>n</italic> = 2,765), GTEx v7 blood (<italic>n</italic> = 338) and lung (<italic>n</italic> = 278) eQTL data, Geuvadis lymphoblastoid cells eQTL data, LBC-BSGS blood mQTL data (<italic>n</italic> = 1,980), and Hannon blood mQTL summary data (<italic>n</italic> = 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.</p><p><bold>Results:</bold> Our SMR analyses identified seven protein-coding genes (<italic>TYK2, IFNAR2, OAS1, OAS3, XCR1, CCR5</italic>, and <italic>MAPT</italic>) associated with COVID-19, including two novel risk genes, <italic>CCR5</italic> and tau-encoding <italic>MAPT</italic>. The TWAS revealed four genes for COVID-19 (<italic>CXCR6, CCR5, CCR9</italic>, and <italic>PIGN</italic>), including two novel risk genes, <italic>CCR5</italic> and <italic>PIGN</italic>.</p><p><bold>Conclusion:</bold> 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.</p>