Multiancestry sex-stratified genomic associations with HIV viral load and controller status from the ICGH.
Details
Serval ID
serval:BIB_18D55776D514
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Multiancestry sex-stratified genomic associations with HIV viral load and controller status from the ICGH.
Journal
JCI insight
Working group(s)
International Collaboration for the Genomics of HIV (ICGH)
ISSN
2379-3708 (Electronic)
ISSN-L
2379-3708
Publication state
Published
Issued date
08/06/2023
Peer-reviewed
Oui
Volume
8
Number
11
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
Publication Status: epublish
Publication Status: epublish
Abstract
Biological sex and host genetics influence HIV pathogenesis. Females have a higher likelihood of spontaneous viral control and lower set point viral load (spVL). No prior studies have assessed sex-specific genetics of HIV. To address this, we performed a sex-stratified genome-wide association study using data from the ICGH. Although it is the largest collection of genomic data in HIV, this multiethnic sample of 9,705 people is 81.3% male. We sought to identify sex-specific genetic variants and genes associated with HIV spVL and control. We confirmed associations in the HLA and CCR5 regions in males and HLA in females. Gene-based analyses detected associations between HIV spVL and PET100, PCP2, XAB2, and STXBP2 only in males. We detected variants with a significant sex-differential effect on spVL in SDC3 and PUM1 (rs10914268) and PSORS1C2 (rs1265159) and on HIV control in SUB1 (rs687659), AL158151.3, PTPA, and IER5L (rs4387067). Those variants have epigenetic and genetic interactions with relevant genes with both cis and trans effects. In summary, we identified sex-shared associations at the single-variant level, sex-specific associations at the gene-based level, and genetic variants with significant differential effects between the sexes.
Keywords
Female, Humans, Male, HIV Infections/genetics, HIV-1/genetics, Viral Load/genetics, Genome-Wide Association Study, Genomics, RNA-Binding Proteins/genetics, AIDS/HIV, Adaptive immunity, Complex traits, Genetic variation, Genetics
Pubmed
Web of science
Open Access
Yes
Create date
01/05/2023 8:10
Last modification date
08/08/2024 6:30