King's College London
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Scripts to perform the GWAS meta-analysis of HIV-1 acquisition and TWAS - Duarte et al. 2022

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posted on 2022-07-21, 12:43 authored by Rodrigo Rafagnin DuarteRodrigo Rafagnin Duarte

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


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.