“The Behavioral, Cellular and Immune Mediators of HIV-1 Acquisition: New Insights from Population Genetics”, 2020-02-24 (; similar):
Millions are exposed to the human immunodeficiency virus type 1 (HIV-1) every year, but not all acquire the virus, suggesting a potential role for host genetics in the moderation of HIV-1 acquisition. Here, we analyzed summary statistics from the largest genome-wide association study of HIV-1 acquisition to-date, consisting of 6,334 infected patients and 7,247 population controls, to advance our understanding of the genetic mechanisms implicated in this trait.
We found that HIV-1 acquisition is polygenic and heritable, with SNP heritability estimates explaining 28–42% of the variance in this trait at a population level. Genetic correlations alongside UK Biobank data revealed associations with smoking, prospective memory, and socioeconomic traits. Gene-level enrichment analysis identified EF-hand calcium-binding domain 14 as a novel susceptibility gene for HIV-1 acquisition. We also observed that susceptibility variants for HIV-1 acquisition were statistically-significantly enriched for genes expressed in T-cells, but also in striatal and hippocampal neurons.
Finally, we tested how polygenic risk scores for HIV-1 acquisition influence blood levels of 35 inflammatory markers in 406 HIV-1-negative individuals. We found that higher genetic risk for HIV-1 acquisition was associated with lower levels of C-C motif chemokine ligand 17.
Our findings corroborate a complex model for HIV-1 acquisition, whereby susceptibility is partly heritable and moderated by specific behavioral, cellular, and immunological parameters.