Host Genetic Factors Associated with Vaginal Microbiome Composition in Kenyan Women

ABSTRACT Bacterial vaginosis (BV) affects 20% of women worldwide and is associated with adverse reproductive health outcomes and increased risk for HIV. Typically, BV represents a shift in the vaginal microbiome from one that is dominated by Lactobacillus to one that is diverse. Persistent racial di...

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Autores principales:	Supriya D. Mehta, Drew R. Nannini, Fredrick Otieno, Stefan J. Green, Walter Agingu, Alan Landay, Yinan Zheng, Lifang Hou
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	vaginal microbiome vaginal microbiota bacterial vaginosis Gardnerella vaginalis Lactobacillus crispatus Lactobacillus iners Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/55a676e94a564afe9d3a9168c534e70e
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spelling	oai:doaj.org-article:55a676e94a564afe9d3a9168c534e70e2021-12-02T18:15:46ZHost Genetic Factors Associated with Vaginal Microbiome Composition in Kenyan Women10.1128/mSystems.00502-202379-5077https://doaj.org/article/55a676e94a564afe9d3a9168c534e70e2020-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSystems.00502-20https://doaj.org/toc/2379-5077ABSTRACT Bacterial vaginosis (BV) affects 20% of women worldwide and is associated with adverse reproductive health outcomes and increased risk for HIV. Typically, BV represents a shift in the vaginal microbiome from one that is dominated by Lactobacillus to one that is diverse. Persistent racial differences in BV and diverse vaginal microbiome composition overlap with racial disparities in risks for HIV and sexually transmitted infection, especially among women of African descent. Risk factors for BV and nonoptimal vaginal microbiome include sexual practices, yet racial differences persist when adjusted for behavioral factors, suggesting a host genetic component. Here, we perform a genome-wide association study on vaginal microbiome traits in Kenyan women. Linear regression and logistic regression were performed, adjusting for age and principal components of genetic ancestry, to evaluate the association between Lactobacillus crispatus, Lactobacillus iners, Gardnerella vaginalis, Shannon diversity index, and community state type (CST) with host genetic single nucleotide polymorphisms (SNPs). We identified novel genomic loci associated with the vaginal microbiome traits, though no SNP reached genome-wide significance. During pathway enrichment analysis, Toll-like receptors (TLRs), cytokine production, and other components of innate immune response were associated with L. crispatus, L. iners, and CST. Multiple previously reported genomic loci were replicated, including IL-8 (Shannon, CST), TIRAP (L. iners, Shannon), TLR2 (Shannon, CST), MBL2 (L. iners, G. vaginalis, CST), and MYD88 (L. iners, Shannon). These genetic associations suggest a role for the innate immune system and cell signaling in vaginal microbiome composition and susceptibility to nonoptimal vaginal microbiome. IMPORTANCE Globally, bacterial vaginosis (BV) is a common condition in women. BV is associated with poorer reproductive health outcomes and HIV risk. Typically, BV represents a shift in the vaginal microbiome from one that is dominated by Lactobacillus to one that is diverse. Despite many women having similar exposures, the prevalence of BV and nonoptimal vaginal microbiome is increased for women of African descent, suggesting a possible role for host genetics. We conducted a genome-wide association study of important vaginal microbiome traits in Kenyan women. We identified novel genetic loci and biological pathways related to mucosal immunity, cell signaling, and infection that were associated with vaginal microbiome traits; we replicated previously reported loci associated with mucosal immune response. These results provide insight into potential host genetic influences on vaginal microbiome composition and can guide larger longitudinal studies, with genetic and functional comparison across microbiome sites within individuals and across populations.Supriya D. MehtaDrew R. NanniniFredrick OtienoStefan J. GreenWalter AginguAlan LandayYinan ZhengLifang HouAmerican Society for Microbiologyarticlevaginal microbiomevaginal microbiotabacterial vaginosisGardnerella vaginalisLactobacillus crispatusLactobacillus inersMicrobiologyQR1-502ENmSystems, Vol 5, Iss 4 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	vaginal microbiome vaginal microbiota bacterial vaginosis Gardnerella vaginalis Lactobacillus crispatus Lactobacillus iners Microbiology QR1-502
spellingShingle	vaginal microbiome vaginal microbiota bacterial vaginosis Gardnerella vaginalis Lactobacillus crispatus Lactobacillus iners Microbiology QR1-502 Supriya D. Mehta Drew R. Nannini Fredrick Otieno Stefan J. Green Walter Agingu Alan Landay Yinan Zheng Lifang Hou Host Genetic Factors Associated with Vaginal Microbiome Composition in Kenyan Women
description	ABSTRACT Bacterial vaginosis (BV) affects 20% of women worldwide and is associated with adverse reproductive health outcomes and increased risk for HIV. Typically, BV represents a shift in the vaginal microbiome from one that is dominated by Lactobacillus to one that is diverse. Persistent racial differences in BV and diverse vaginal microbiome composition overlap with racial disparities in risks for HIV and sexually transmitted infection, especially among women of African descent. Risk factors for BV and nonoptimal vaginal microbiome include sexual practices, yet racial differences persist when adjusted for behavioral factors, suggesting a host genetic component. Here, we perform a genome-wide association study on vaginal microbiome traits in Kenyan women. Linear regression and logistic regression were performed, adjusting for age and principal components of genetic ancestry, to evaluate the association between Lactobacillus crispatus, Lactobacillus iners, Gardnerella vaginalis, Shannon diversity index, and community state type (CST) with host genetic single nucleotide polymorphisms (SNPs). We identified novel genomic loci associated with the vaginal microbiome traits, though no SNP reached genome-wide significance. During pathway enrichment analysis, Toll-like receptors (TLRs), cytokine production, and other components of innate immune response were associated with L. crispatus, L. iners, and CST. Multiple previously reported genomic loci were replicated, including IL-8 (Shannon, CST), TIRAP (L. iners, Shannon), TLR2 (Shannon, CST), MBL2 (L. iners, G. vaginalis, CST), and MYD88 (L. iners, Shannon). These genetic associations suggest a role for the innate immune system and cell signaling in vaginal microbiome composition and susceptibility to nonoptimal vaginal microbiome. IMPORTANCE Globally, bacterial vaginosis (BV) is a common condition in women. BV is associated with poorer reproductive health outcomes and HIV risk. Typically, BV represents a shift in the vaginal microbiome from one that is dominated by Lactobacillus to one that is diverse. Despite many women having similar exposures, the prevalence of BV and nonoptimal vaginal microbiome is increased for women of African descent, suggesting a possible role for host genetics. We conducted a genome-wide association study of important vaginal microbiome traits in Kenyan women. We identified novel genetic loci and biological pathways related to mucosal immunity, cell signaling, and infection that were associated with vaginal microbiome traits; we replicated previously reported loci associated with mucosal immune response. These results provide insight into potential host genetic influences on vaginal microbiome composition and can guide larger longitudinal studies, with genetic and functional comparison across microbiome sites within individuals and across populations.
format	article
author	Supriya D. Mehta Drew R. Nannini Fredrick Otieno Stefan J. Green Walter Agingu Alan Landay Yinan Zheng Lifang Hou
author_facet	Supriya D. Mehta Drew R. Nannini Fredrick Otieno Stefan J. Green Walter Agingu Alan Landay Yinan Zheng Lifang Hou
author_sort	Supriya D. Mehta
title	Host Genetic Factors Associated with Vaginal Microbiome Composition in Kenyan Women
title_short	Host Genetic Factors Associated with Vaginal Microbiome Composition in Kenyan Women
title_full	Host Genetic Factors Associated with Vaginal Microbiome Composition in Kenyan Women
title_fullStr	Host Genetic Factors Associated with Vaginal Microbiome Composition in Kenyan Women
title_full_unstemmed	Host Genetic Factors Associated with Vaginal Microbiome Composition in Kenyan Women
title_sort	host genetic factors associated with vaginal microbiome composition in kenyan women
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/55a676e94a564afe9d3a9168c534e70e
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Host Genetic Factors Associated with Vaginal Microbiome Composition in Kenyan Women

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