Evaluating the impact of functional genetic variation on HIV-1 control.  Journal of Infectious Diseases
Human genetic variation plays a large role in determining the outcome of HIV-1 infection. However, common, genome-wide genetic factors identified by genome-wide association studies can only explain up to 25% of the observed variability in HIV setpoint viral load.
To assess the evidence for an additional impact of functional variation in HIV progression, McLaren et al. combined exome sequence data across 5 independent studies that evaluated 3 related models of HIV control in a total of 1’327 individuals with high-quality data.
The authors found that multiple single variants within the major histocompatibility complex (MHC) region were observed to be strongly associated with HIV-1 outcome, consistent with the known impact of classical HLA alleles. However, no single variant or gene located outside of the MHC region was significantly associated with HIV progression. Set-based association testing focusing on genes identified as being essential for HIV replication in genome-wide small interfering RNA and clustered regularly interspaced short palindromic repeats (CRISPR) studies did not reveal any novel associations.
In conclusion, the study-results suggest that exomic variants with large effect sizes are unlikely to have a major contribution to host control of HIV infection.