COVID-19 and Indian population: a comparative genetic analysis

Abstract

ABSTRACTBackgroundMajor risk factors of COVID-19 include older age, male gender, and comorbidities. In addition, host genetic makeup is also known to play a major role in COVID-19 susceptibility and severity. To assess the genetic predisposition of the Indian population to COVID-19, a comparative analysis of the frequencies of polymorphisms directly or potentially associated with COVID-19 susceptibility, severity, immune response, and fatal outcomes was done between the Indian population and other major populations (European, African, East Asian, South Asian, and American).Materials and methodsPolymorphisms directly or potentially associated with COVID-19 susceptibility, severity, immune response, and mortality were mined from genetic association studies, comparative genetic studies, expression quantitative trait loci studies among others. Genotype data of these polymorphisms were either sourced from the GenomegaDB™ database of Mapmygenome India Ltd. (sample size = 3054; Indian origin) or were imputed. Polymorphisms with minor allele frequency >= 0.05 and that are in Hardy-Weinberg equilibrium in the Indian population were considered for allele frequency comparison between the Indian population and 1000 Genome population groups.ResultsAllele frequencies of 421 polymorphisms were found to be significantly different in the Indian population compared to European, African, East Asian, South Asian, and American populations. 128 polymorphisms were shortlisted based on linkage disequilibrium and were analyzed in detail. Apart from well-studied genes, like ACE2, TMPRSS2, ADAM17, and FURIN, variants from AHSG, IFITM3, PTPN2, CD209, CCL5, HEATR9, SELENBP9, AGO1, HLA-G, MX1, ICAM3, MUC5B, CRP, C1GALT1, and other genes were also found to be significantly different in Indian population. These variants might be implicated in COVID-19 susceptibility and progression.ConclusionOur comparative study unraveled multiple genetic variants whose allele frequencies were significantly different in the Indian population and might have a potential role in COVID-19 susceptibility, its severity, and fatal outcomes. This study can be very useful for selecting candidate genes/variants for future COVID-19 related genetic association studies.