2017-11-27Zeitschriftenartikel DOI: 10.1093/infdis/jix470
Evaluating the Impact of Functional Genetic Variation on HIV-1 Control
McLaren, Paul J.
Pulit, Sara L.
Shea, Patrick R.
Young, Elizabeth H.
Amo, Julia Del
Gill, M. John
Kelleher, Anthony D.
Post, Frank A.
Haas, David W.
Walker, Bruce D.
Goldstein, David B.
Sandhu, Manjinder S.
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.
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