McLaren, Paul JPulit, Sara LGurdasani, DeeptiBartha, IstvanShea, Patrick RPomilla, CristinaGupta, NamrataGkrania-Klotsas, EffrossyniYoung, Elizabeth HBannert, NorbertDel Amo, JuliaGill, M JohnGilmour, JillKellam, PaulKelleher, Anthony DSönnerborg, AndersZangerle, RobertPost, Frank AFisher, MartinHaas, David WWalker, BrucePorter, KholoudGoldstein, David BSandhu, Manjinder Sde Bakker, Paul I WFellay, Jacques2018-04-192017McLaren, P. J., S. L. Pulit, D. Gurdasani, I. Bartha, P. R. Shea, C. Pomilla, N. Gupta, et al. 2017. “Evaluating the Impact of Functional Genetic Variation on HIV-1 Control.” The Journal of Infectious Diseases 216 (9): 1063-1069. doi:10.1093/infdis/jix470. http://dx.doi.org/10.1093/infdis/jix470.http://nrs.harvard.edu/urn-3:HUL.InstRepos:35982148Abstract 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.en-USHIV/AIDSHIV-1 controlexome sequencingHIV-1 progressionhost genetics of infectionHIV host dependency factorsJournal Article2018-04-1910.1093/infdis/jix470