Enrichment analysis of polymorphic loci associated with SARS-CoV-2 infection and its outcomes

Background: There is a relatively long list of polymorphic genes associated with susceptibility to, hospitalization for, severity of, and death from COVID-19. Methods: Enrichment analysis was performed using polymorphic loci retrieved from the Genome-wide association studies (GWAS) database associated with susceptibility to, hospitalization for, severity of, and death from COVID-19. Only protein-coding genes were included in this study. Results: A total of 177, 91, 67, 67, and 22 loci were identified whose genetic polymorphisms were associated with susceptibility to, hospitalization for, severity of, and death from COVID-19, respectively. No significant results were found in the enrichment analysis. The common genes among the different aspects of COVID-19 were low. Susceptibility to, hospitalization for, severity of, and death from COVID-19 shared 39, 22, 19, and 9 loci with smoking initiation trait, respectively. Statistical analysis indicated that the levels of sharing were highly significant. The low number of shared genes among the four sets of susceptibility, hospitalization, disease severity, and death due to COVID-19 suggests that these aspects of COVID-19 are distinct multifactorial traits. Conclusion: It was concluded that factors such as chronic cardiovascular disease and diabetes mellitus are not independent risk factors for COVID-19 and its outcomes, and that smoking is the most important and influential risk factor. Further analysis using Mendelian randomization on the available information is needed to confirm or reject this conclusion.