Genomewide association study for determinants of HIV-1 acquisition and viral set point in HIV-1 serodiscordant couples with quantified virus exposure.

TitleGenomewide association study for determinants of HIV-1 acquisition and viral set point in HIV-1 serodiscordant couples with quantified virus exposure.
Publication TypeJournal Article
Year of Publication2011
AuthorsLingappa JR, Petrovski S, Kahle E, Fellay J, Shianna K, McElrath JM, Thomas KK, Baeten JM, Celum C, Wald A, de Bruyn G, Mullins JI, Nakku-Joloba E, Farquhar C, Essex M, Donnell D, Kiarie J, Haynes BF, Goldstein D
Corporate AuthorsPartners in Prevention HSV/HIV Transmission Study Team
JournalPLoS One
Volume6
Issue12
Paginatione28632
Date Published2011
ISSN1932-6203
KeywordsAdolescent, Adult, Africa, Eastern, Aged, Family Characteristics, Female, Genetic Variation, Genome-Wide Association Study, Genotype, HIV Infections, HIV Seropositivity, HIV-1, Humans, Male, Middle Aged, Young Adult
Abstract

BACKGROUND: Host genetic factors may be important determinants of HIV-1 sexual acquisition. We performed a genome-wide association study (GWAS) for host genetic variants modifying HIV-1 acquisition and viral control in the context of a cohort of African HIV-1 serodiscordant heterosexual couples. To minimize misclassification of HIV-1 risk, we quantified HIV-1 exposure, using data including plasma HIV-1 concentrations, gender, and condom use.

METHODS: We matched couples without HIV-1 seroconversion to those with seroconversion by quantified HIV-1 exposure risk. Logistic regression of single nucleotide polymorphisms (SNPs) for 798 samples from 496 HIV-1 infected and 302 HIV-1 exposed, uninfected individuals was performed to identify factors associated with HIV-1 acquisition. In addition, a linear regression analysis was performed using SNP data from a subset (n = 403) of HIV-1 infected individuals to identify factors predicting plasma HIV-1 concentrations.

RESULTS: After correcting for multiple comparisons, no SNPs were significantly associated with HIV-1 infection status or plasma HIV-1 concentrations.

CONCLUSION: This GWAS controlling for HIV-1 exposure did not identify common host genotypes influencing HIV-1 acquisition. Alternative strategies, such as large-scale sequencing to identify low frequency variation, should be considered for identifying novel host genetic predictors of HIV-1 acquisition.

DOI10.1371/journal.pone.0028632
Alternate JournalPLoS ONE
PubMed ID22174851