Novel genetic locus implicated for HIV-1 acquisition with putative regulatory links to HIV replication and infectivity: a genome-wide association study

PloS One
Eric O JohnsonAlex H Kral

Abstract

Fifty percent of variability in HIV-1 susceptibility is attributable to host genetics. Thus identifying genetic associations is essential to understanding pathogenesis of HIV-1 and important for targeting drug development. To date, however, CCR5 remains the only gene conclusively associated with HIV acquisition. To identify novel host genetic determinants of HIV-1 acquisition, we conducted a genome-wide association study among a high-risk sample of 3,136 injection drug users (IDUs) from the Urban Health Study (UHS). In addition to being IDUs, HIV-controls were frequency-matched to cases on environmental exposures to enhance detection of genetic effects. We tested independent replication in the Women's Interagency HIV Study (N=2,533). We also examined publicly available gene expression data to link SNPs associated with HIV acquisition to known mechanisms affecting HIV replication/infectivity. Analysis of the UHS nominated eight genetic regions for replication testing. SNP rs4878712 in FRMPD1 met multiple testing correction for independent replication (P=1.38x10(-4)), although the UHS-WIHS meta-analysis p-value did not reach genome-wide significance (P=4.47x10(-7) vs. P<5.0x10(-8)) Gene expression analyses provided promising biol...Continue Reading

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Citations

Sep 19, 2015·Genes, Brain, and Behavior·D B HancockE O Johnson
Dec 19, 2016·American Journal of Human Genetics·Ari V Ahola-OlliOlli T Raitakari
May 16, 2020·Human Genetics·Shanelle N GingrasPaul J McLaren
Jul 12, 2017·Immunogenetics·Vivek Naranbhai, Mary Carrington
Feb 8, 2019·Frontiers in Genetics·Riley H Tough, Paul J McLaren
Feb 25, 2019·European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology·Junpeng ZhaoLunan Wang
Oct 2, 2019·Frontiers in Genetics·Sigrid Le ClercJean-François Zagury
Nov 7, 2017·PLoS Pathogens·Romel D MackelprangUNKNOWN Partners in Prevention HSV/HIV Transmission Study and the Partners PrEP Study Teams
Dec 6, 2020·Nature Reviews. Genetics·Andrew J KwokJulian C Knight

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Methods Mentioned

BETA
Genotyping
RNAseq

Software Mentioned

IMPUTE2
METAL
MuTHER
HaploReg loci ( eQTL ) browser
Genevar

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