文章基本信息

标题：Transcriptome-wide association study of HIV-1 acquisition identifies HERC1 as a susceptibility gene
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作者：Rodrigo R.R. Duarte ; Oliver Pain ; Robert L. Furler 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2022
卷号：25
期号：9
页码：1-17
DOI：10.1016/j.isci.2022.104854
语种：English
出版社：Elsevier
摘要：SummaryThe 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, includingHERC1,UEVLD, andHIST1H4K. Convergent evidence from conditional analyses and fine-mapping identifiedHERC1downregulation in immune cells as a robust mechanism associated with HIV-1 acquisition. Functional studies onHERC1and 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.Graphical abstractDisplay OmittedHighlights•HIV-1 acquisition is highly polygenic, with a SNP heritability estimate of 21%•HIV-1 acquisition correlates with behavioral factors such as smoking•HERC1downregulation in immune cells is associated with HIV-1 acquisition riskGenetics; Immunity; Bioinformatics