GWAS Summary statistics - HIV-1 acquisition meta-analysis - Duarte et al. 2022
Transcriptome-wide association study of HIV-1 acquisition identifies HERC1 as a susceptibility gene
Abstract: The host genetic factors conferring protection against HIV-1 acquisition, particularly those regulated by common genetic variants, remain elusive. 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.
Content: The file in this repository contains GWAS summary statistics for the HIV-1 meta-analysis and a read me file describing the column labels.
Studies included in the meta-analysis (see URLs under "References"):
1) McLaren P.J. et al. (2013). Association Study of Common Genetic Variants and HIV-1 Acquisition in 6,300 Infected Cases and 7,200 Controls. PLOS Pathogens 9, e1003515. 10.1371/journal.ppat.1003515.
2) Johnson E.O. et al. (2015). Novel Genetic Locus Implicated for HIV-1 Acquisition with Putative Regulatory Links to HIV Replication and Infectivity: A Genome-Wide Association Study. PLOS ONE 10, e0118149. 10.1371/journal.pone.0118149.
3) Ben Neale’s group’s UKBB results (data release 3, trait ID 20002_1439 HIV/AIDS).
4) FinnGen (data release 5, trait ID AB1_HIV).
Related content: Code used in manuscript has also been deposited in Figshare, DOI: 10.18742/20343219.
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Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award number R21 AI154956. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.