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GWAS Study

Transcriptome-wide association study of HIV-1 acquisition identifies <i>HERC1</i> as a susceptibility gene.

Duarte RRR, Pain O, Furler RL et al.

36034232 PubMed ID
GWAS Study Type
594646 Participants
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Chapter I

Publication Details

Comprehensive information about this research publication

Authors

DR
Duarte RRR
PO
Pain O
FR
Furler RL
ND
Nixon DF
PT
Powell TR
Chapter II

Abstract

Summary of the research findings

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.

7,303 European ancestry cases, 587,343 European ancestry controls

Chapter III

Study Statistics

Key metrics and study information

594646
Total Participants
GWAS
Study Type
No
Replicated
European
Ancestry
U.K.
Recruitment Country
Chapter IV

Analysis

Comprehensive review of health and genetic findings

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