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- W4289755510 abstract "The host genetic factors conferring protection against HIV type 1 (HIV-1) acquisition remain elusive, and in particular the contributions of common genetic variants. Here, we performed the largest genome-wide association meta-analysis of HIV-1 acquisition, which included 7,303 HIV-1-positive individuals and 587,343 population controls. We identified 25 independent genetic loci with suggestive association, of which one was genome-wide significant within the major histocompatibility complex (MHC) locus. After exclusion of the MHC signal, linkage disequilibrium score regression analyses revealed a SNP heritability of 21% and genetic correlations with behavioral factors. A transcriptome-wide association study identified 15 susceptibility genes, including HERC1, UEVLD, and HIST1H4K. Convergent evidence from conditional analyses and fine-mapping identified HERC1 downregulation in immune cells as a robust mechanism associated with HIV-1 acquisition. Functional studies on HERC1 and other identified candidates, as well as larger genetic studies, have the potential to further our understanding of the host mechanisms associated with protection against HIV-1." @default.
- W4289755510 created "2022-08-04" @default.
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- W4289755510 date "2022-09-01" @default.
- W4289755510 modified "2023-09-26" @default.
- W4289755510 title "Transcriptome-wide association study of HIV-1 acquisition identifies HERC1 as a susceptibility gene" @default.
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- W4289755510 doi "https://doi.org/10.1016/j.isci.2022.104854" @default.
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