Novel Genetic Locus Implicated for HIV-1 Acquisition with Putative Regulatory Links to HIV Replication and Infectivity: A Genome-Wide Association Study

Eric O Johnson, Dana B Hancock, Nathan C Gaddis, Joshua L Levy, Grier Page, Scott P Novak, Cristie Glasheen, Nancy L Saccone, John P Rice, Michael P Moreau, Kimberly F Doheny, Jane M Romm, Andrew I Brooks, Bradley E Aouizerat, Laura J Bierut and Alex H Kral

PLOS ONE, 2015, vol. 10, issue 3, 1-15

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

Date: 2015
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0118149

DOI: 10.1371/journal.pone.0118149

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