|Title||Genomewide association study for determinants of HIV-1 acquisition and viral set point in HIV-1 serodiscordant couples with quantified virus exposure.|
|Publication Type||Journal Article|
|Year of Publication||2011|
|Authors||Lingappa 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 Authors||Partners in Prevention HSV/HIV Transmission Study Team|
|Keywords||Adolescent, 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|
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.
|Alternate Journal||PLoS ONE|