Exome-wide association study for replication of rare variants affecting the severity of COVID-19 in the Russian population

Abstract

BACKGROUND: Human genotype is a factor that determines the severity of COVID-19. Previously, a large-scale whole-genome association study of the COVID-19 Host Genetics Initiative (2021) investigated the association of genetic variants at multiple loci with COVID-19 severity. The genetic variants that have the greatest effect on COVID-19 severity are expected to have a low frequency in the population. Therefore, the study of rare variants may provide additional insights into the disease pathogenesis and thus help in the development of prevention and treatment options. AIM: To search for genes enriched for rare genetic variants associated with COVID-19 severity in the Russian population by replication analysis. METHODS: The clinical exome of a Russian cohort of patients was sequenced based on the St. Petersburg State Budgetary Institution “City Hospital No. 40” and St Petersburg University. The study used biomaterial from patients hospitalized at City Hospital No. 40 diagnosed with COVID-19 and healthy individuals (population control group). The severity of the course of COVID-19 was determined according to the results of lung computed tomography. The list of genes for subsequent replication was generated by a literature review. Burden test methods were used for the replication analysis of genes associated with COVID-19 severity. RESULTS: In total, 701 clinical exomes were sequenced from 263 individuals with severe COVID-19 and 438 healthy individuals. In the literature review, 18 genes associated with severe COVID-19 were included in the replication analysis. The replication analysis did not identify any genes whose association with severe COVID-19 was confirmed in the study cohort. CONCLUSION: The replication analysis did not identify any genes that showed a significant association between the functional variant enrichment and COVID-19 severity. However, the direction of the correlation was consistent with the findings of previous studies. Expanding the study cohort would increase the power of the tests and allow us to detect additional rare variants that influence the severity of COVID-19 progression.