Evaluating the Impact of Functional Genetic Variation on HIV-1 Control.

ABSTRACT: Background:Previous genetic association studies of human immunodeficiency virus-1 (HIV-1) progression have focused on common human genetic variation ascertained through genome-wide genotyping. Methods:We sought to systematically assess the full spectrum of functional variation in protein coding gene regions on HIV-1 progression through exome sequencing of 1327 individuals. Genetic variants were tested individually and in aggregate across genes and gene sets for an influence on HIV-1 viral load. Results:Multiple single variants within the major histocompatibility complex (MHC) region were observed to be strongly associated with HIV-1 outcome, consistent with the known impact of classical HLA alleles. However, no single variant or gene located outside of the MHC region was significantly associated with HIV progression. Set-based association testing focusing on genes identified as being essential for HIV replication in genome-wide small interfering RNA (siRNA) and clustered regularly interspaced short palindromic repeats (CRISPR) studies did not reveal any novel associations. Conclusions:These results suggest that exonic variants with large effect sizes are unlikely to have a major contribution to host control of HIV infection.

SUBMITTER: McLaren PJ 

PROVIDER: S-EPMC5853944 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature