The behavioral, cellular and immune mediators of HIV-1 acquisition: New insights from population genetics
Abstract 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...
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| Autores principales: | , , , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Nature Portfolio
2020
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/4d125614518f49bc8192fd1c6c270373 |
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| Sumario: | Abstract 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 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. |
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