TY - GEN T1 - Evaluating the Impact of Functional Genetic Variation on HIV-1 Control AU - McLaren, Paul J. AU - Pulit, Sara L. AU - Gurdasani, Deepti AU - Bartha, Istvan AU - Shea, Patrick R. AU - Pomilla, Cristina AU - Gupta, Namrata AU - Gkrania-Klotsas, Effrossyni AU - Young, Elizabeth H. AU - Bannert, Norbert AU - Amo, Julia Del AU - Gill, M. John AU - Gilmour, Jill AU - Kellam, Paul AU - Kelleher, Anthony D. AU - Sönnerborg, Anders AU - Zangerle, Robert AU - Post, Frank A. AU - Fisher, Martin AU - Haas, David W. AU - Walker, Bruce D. AU - Porter, Kholoud AU - Goldstein, David B. AU - Sandhu, Manjinder S. AU - Fellay, Jacques AB - 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. KW - Single Nucleotide KW - Humans KW - Female KW - Male KW - Adult KW - Middle Aged KW - Genetic Predisposition to Disease KW - HIV Infections/virology KW - Genotype KW - HIV-1/genetics KW - Genetic Variation KW - Polymorphism KW - HIV Infections/genetics KW - Host-Pathogen Interactions/genetics KW - Viral Load/genetics KW - Whole Exome Sequencing KW - 610 Medizin PY - 2017 LA - ger PB - Robert Koch-Institut, Infektionskrankheiten / Erreger VL - 216 IS - 9 DO - 10.1093/infdis/jix470 ER -