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

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.

Figure 1. Manhattan plot for analysis of HIV-1 acquisition.

-log₁₀(p) is plotted for all SNPs against physical location of each SNP in the genome (listed by chromosome number 1 through 22, and X and XY). The threshold for genome-wide significance (P = 5.1×10⁻⁸) is indicated.

Figure 2. Manhattan plot for analysis of plasma HIV-1 set point.

-log₁₀(p) is plotted for all SNPs against physical location of each SNP in the genome (listed by chromosome number 1 through 22, and X and XY). The threshold for genome-wide significance is indicated.