Genome-wide identification of susceptibility alleles for viral infections through a population genetics approach

Viruses have exerted a constant and potent selective pressure on human genes throughout evolution. we utilized the marks left by selection on allele frequency to identify viral infection-associated allelic variants. virus diversity (the number of different viruses in a geographic region) was used to measure virus-driven selective pressure. results showed an excess of variants correlated with virus diversity in genes involved in immune response and in the biosynthesis of glycan structures functioning as viral receptors; a significantly higher than expected number of variants was also seen in genes encoding proteins that directly interact with viral components. genome-wide analyses identified 441 variants significantly associated with virus-diversity; these are more frequently located within gene regions than expected,and they map to 139 human genes. analysis of functional relationships among genes subjected to virus-driven selective pressure identified a complex network enriched in viral products-interacting proteins. the novel approach to the study of infectious disease epidemiology presented herein may represent an alternative to classic genome-wide association studies and provides a large set of candidate susceptibility variants for viral infections. © 2010 fumagalli et al.