Fan Wei, Kan Hui, Liu Hai-Yan, Wang Tian-Lei, He Yi-Ning, Zhang Miao, Li Ya-Xin, Li Yi-Jie, Meng Wei, Li Qing, Hu An-Qun, Zheng Ying-Jie
Department of Epidemiology, Fudan Universitygrid.8547.e, Shanghai, China.
Key Laboratory for Health Technology Assessment, National Commission of Health and Family Planning, Fudan Universitygrid.8547.e, Shanghai, China.
mSystems. 2021 Aug 31;6(4):e0015821. doi: 10.1128/mSystems.00158-21. Epub 2021 Jul 20.
The influence of human genetic variants on the vaginal bacterial traits (VBTs) of pregnant women is still unknown. Using a genome-wide association approach based on the 16S rRNA bacteriome analysis, a total of 72 host genetic variant (single nucleotide polymorphisms [SNPs], indels, or copy number variations [CNVs])-VBT associations were found that reached the genome-wide significance level ( < 5 × 10) with an acceptable genomic inflation factor λ of <1.1. The majority of these SNPs that reached the genome-wide significance level had a relatively low minor allele frequency (MAF), and only seven of them had MAFs greater than 0.05. rs303212, located at the IFIT1 gene on chromosome 10, was the most eye-catching variant, which had a genome-wide association with the relative abundance (RAB) of and and also had a suggestive association with the RAB of a few common vaginal bacteria including , , , and Gardnerella vaginalis and the beta diversity weighted UniFrac ( < 1 × 10). The findings of the study suggest that the vaginal bacteriome may be influenced by a number of genetic variants across the human genome and that interferon signaling may have an important influence on vaginal bacterial communities during pregnancy. Knowledge about the influence of host genetics on the vaginal bacteriome in pregnancy is still limited. Although a number of environmental and behavioral factors may exert influences on the structure of vaginal bacterial communities, the vaginal bacteriome often undergoes a relatively fixed transition to a more stable and less diverse state as the menstrual cycle stops, which raises questions on the effects of human genetics. We utilized a genome-wide approach to identify the associations between genetic variants and multiple VBTs and performed enrichment analyses. The human genetics during pregnancy may be involved in multiple pathways. The results may disclose innate functional factors involved in shaping the vaginal bacteriome during pregnancy and provide insight into the establishment of specific strategies for prevention and clinical treatment of pregnancy complications.
人类基因变异对孕妇阴道细菌特征（VBTs）的影响尚不清楚。采用基于16S rRNA细菌群落分析的全基因组关联方法，共发现72种宿主基因变异（单核苷酸多态性[SNP]、插入缺失或拷贝数变异[CNV]）与VBT的关联达到全基因组显著性水平（<5×10），且基因组膨胀因子λ<1.1，在可接受范围内。这些达到全基因组显著性水平的SNP大多具有相对较低的次要等位基因频率（MAF），其中只有7个MAF大于0.05。位于10号染色体上IFIT1基因的rs303212是最引人注目的变异，它与 和 的相对丰度（RAB）存在全基因组关联，也与一些常见阴道细菌（包括 、 、 及阴道加德纳菌）的RAB以及β多样性加权UniFrac存在提示性关联（<1×10）。该研究结果表明，阴道细菌群落可能受到人类基因组中多个基因变异的影响，且干扰素信号传导可能在孕期对阴道细菌群落有重要影响。关于宿主基因对孕期阴道细菌群落的影响的知识仍然有限。尽管许多环境和行为因素可能会影响阴道细菌群落的结构，但随着月经周期停止，阴道细菌群落通常会经历相对固定的转变，进入更稳定、多样性更低的状态，这引发了关于人类基因影响的疑问。我们采用全基因组方法来识别基因变异与多种VBT之间的关联，并进行了富集分析。孕期的人类基因可能涉及多个途径。这些结果可能揭示孕期塑造阴道细菌群落的内在功能因素，并为预防和临床治疗妊娠并发症的具体策略的制定提供见解。
