Scripts to perform the GWAS meta-analysis of HIV-1 acquisition and TWAS - 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 files in this repository correspond to all scripts used for performing the meta-analysis and TWAS detailed in this paper. Related content: GWAS summary statistics (HIV-1 acquisition) has also been deposited in Figshare, DOI: 10.18742/18166406. Disclaimer: If you choose to download and use these scripts, you acknowledge that: - These are provided on an “as-is” basis, and no warranty is provided as to their performance or fitness for any purpose - You will cite Duarte et al. 2022 in any communications or publications arising directly or indirectly from these scripts