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:	Timothy R. Powell, Rodrigo R. R. Duarte, Matthew Hotopf, Stephani L. Hatch, Miguel de Mulder Rougvie, Gerome D. Breen, Cathryn M. Lewis, Douglas F. Nixon
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4d125614518f49bc8192fd1c6c270373
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spelling	oai:doaj.org-article:4d125614518f49bc8192fd1c6c2703732021-12-02T16:23:09ZThe behavioral, cellular and immune mediators of HIV-1 acquisition: New insights from population genetics10.1038/s41598-020-59256-02045-2322https://doaj.org/article/4d125614518f49bc8192fd1c6c2703732020-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-59256-0https://doaj.org/toc/2045-2322Abstract 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.Timothy R. PowellRodrigo R. R. DuarteMatthew HotopfStephani L. HatchMiguel de Mulder RougvieGerome D. BreenCathryn M. LewisDouglas F. NixonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-10 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Timothy R. Powell Rodrigo R. R. Duarte Matthew Hotopf Stephani L. Hatch Miguel de Mulder Rougvie Gerome D. Breen Cathryn M. Lewis Douglas F. Nixon The behavioral, cellular and immune mediators of HIV-1 acquisition: New insights from population genetics
description	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.
format	article
author	Timothy R. Powell Rodrigo R. R. Duarte Matthew Hotopf Stephani L. Hatch Miguel de Mulder Rougvie Gerome D. Breen Cathryn M. Lewis Douglas F. Nixon
author_facet	Timothy R. Powell Rodrigo R. R. Duarte Matthew Hotopf Stephani L. Hatch Miguel de Mulder Rougvie Gerome D. Breen Cathryn M. Lewis Douglas F. Nixon
author_sort	Timothy R. Powell
title	The behavioral, cellular and immune mediators of HIV-1 acquisition: New insights from population genetics
title_short	The behavioral, cellular and immune mediators of HIV-1 acquisition: New insights from population genetics
title_full	The behavioral, cellular and immune mediators of HIV-1 acquisition: New insights from population genetics
title_fullStr	The behavioral, cellular and immune mediators of HIV-1 acquisition: New insights from population genetics
title_full_unstemmed	The behavioral, cellular and immune mediators of HIV-1 acquisition: New insights from population genetics
title_sort	behavioral, cellular and immune mediators of hiv-1 acquisition: new insights from population genetics
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/4d125614518f49bc8192fd1c6c270373
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The behavioral, cellular and immune mediators of HIV-1 acquisition: New insights from population genetics

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