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.
Highlights
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and resultant COVID-19 have created a public health crisis worldwide
A total of 20 genome-wide genes were detected for the COVID-19 Genome-wide association studies (GWASs) (Table 1)
We discovered two genes associated with the lung eQTL dataset (CXCR6 and CCR5) and two genes associated with the blood eQTL dataset (CCR9 and PIGN) (Table 3)
Summary
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and resultant COVID-19 have created a public health crisis worldwide. The majority of infected persons are either affected mildly or stay asymptomatic. It was reported that ∼10–20% of people with COVID-19 infection need hospitalization [1]. Hypertension, obesity, and diabetes are among the common comorbidities of hospitalized patients [2]. Patients with older age or medical complications tend to have severe symptoms. Some young and seemingly healthy individuals may have serious outcomes from the virus infection. Severity, and prognosis of the disease are
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