Host Genetic Factors Associated with Vaginal Microbiome Composition in Kenyan Women
Host Genetic Factors Associated with Vaginal Microbiome Composition in Kenyan Women
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DOI：
10.1128/msystems.00502-20
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发表时间：
2020-07-01
期刊：
影响因子：
6.4
通讯作者：
Hou, Lifang
中科院分区：
文献类型：
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作者：
Mehta, Supriya D.;Nannini, Drew R.;Hou, Lifang
细菌性阴道病 (BV) 影响着全球 20% 的女性，并与不良的生殖健康结果和艾滋病毒风险增加有关。通常，BV 代表阴道微生物组从以乳杆菌为主的微生物组向多样化的微生物组的转变。 BV 和多样化阴道微生物组组成的持续种族差异与艾滋病毒和性传播感染风险的种族差异重叠，特别是在非洲裔女性中。 BV 和非最佳阴道微生物群的危险因素包括性行为，但在调整行为因素后，种族差异仍然存在，这表明存在宿主遗传因素。在这里，我们对肯尼亚女性的阴道微生物组特征进行了全基因组关联研究。进行线性回归和逻辑回归，调整年龄和遗传祖先的主要成分，以评估卷曲乳杆菌、惰性乳杆菌、阴道加德纳菌、香农多样性指数和群落状态类型 (CST) 与宿主遗传单核苷酸多态性 (SNP) 之间的关联。我们鉴定了与阴道微生物组特征相关的新基因组位点，但没有 SNP 达到全基因组显着性。在通路富集分析中，Toll 样受体 (TLR)、细胞因子产生和先天免疫反应的其他组成部分与卷曲乳杆菌、惰性乳杆菌和 CST 相关。复制了多个先前报道的基因组位点，包括 IL-8 (Shannon, CST)、TIRAP (L. iners, Shannon)、TLR2 (Shannon, CST)、MBL2 (L. iners, G. vaginalis, CST) 和 MYD88 (L. iners, Shannon)。这些遗传关联表明先天免疫系统和细胞信号传导在阴道微生物组组成以及对非最佳阴道微生物组的易感性中发挥着作用。 重要性 在全球范围内，细菌性阴道病 (BV) 是女性的常见病症。 BV 与较差的生殖健康结果和艾滋病毒风险相关。通常，BV 代表阴道微生物组从以乳杆菌为主的微生物组向多样化的微生物组的转变。尽管许多女性有类似的暴露情况，但非洲裔女性 BV 和非最佳阴道微生物群的患病率有所增加，这表明宿主遗传学可能发挥作用。我们对肯尼亚女性重要的阴道微生物组特征进行了全基因组关联研究。我们确定了与粘膜免疫、细胞信号传导和感染相关的新基因位点和生物途径，这些基因位点和生物途径与阴道微生物组特征相关；我们复制了之前报道的与粘膜免疫反应相关的位点。这些结果提供了对宿主遗传对阴道微生物组组成的潜在影响的深入了解，并可以指导更大规模的纵向研究，对个体内和人群中的微生物组位点进行遗传和功能比较。
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.