Host genetic variation and its microbiome interactions within the Human Microbiome Project.
Host genetic variation and its microbiome interactions within the Human Microbiome Project.
复制标题
DOI：
10.1186/s13073-018-0515-8
复制
发表时间：
2018-01-29
期刊：
影响因子：
12.3
通讯作者：
Huttenhower C
中科院分区：
文献类型：
--
作者：
Kolde R;Franzosa EA;Rahnavard G;Hall AB;Vlamakis H;Stevens C;Daly MJ;Xavier RJ;Huttenhower C
尽管越来越多的人认识到人体内的微生物群落与健康有关，但我们对塑造这些群落组成的环境和分子相互作用的了解并不完整。尽管宿主遗传因素在这些相互作用中发挥作用，但鉴于需要进行基因分型和微生物组表征的大型人群队列，这些因素相对尚未探索。我们对来自人类微生物组计划（HMP）健康队列研究的298名供体进行了全基因组测序，以伴随其在不同身体部位的微生物组的现有深入表征。该分析产生了32倍的平均测序深度，我们鉴定了2700万（M）个单核苷酸变体和2.3M个插入-缺失。微生物组的分类组成和功能潜力与胃肠道和口腔群落中的遗传主要成分显着共变，但在鼻孔或阴道微生物群中则不然。相关性的例子包括验证FUT 2分泌状态以及LCT基因附近的乳酸转运减少的变体与粪便中长双歧杆菌丰度之间的已知关联。微生物特征与高水平遗传属性和单一变体的关联特定于特定的身体部位，突出了在多个身体部位的微生物群落中找到控制微生物组特性的独特遗传机制的机会。这项研究将宿主基因组的深度测序添加到HMP健康队列中已经存在的全身微生物组序列中，为未来寻求识别微生物组宿主遗传调节剂的研究创造了一个独特的，通用的和良好控制的参考。本文的在线版本（10.1186/s13073-018-0515-8）包含补充材料，可供授权用户使用。
Despite the increasing recognition that microbial communities within the human body are linked to health, we have an incomplete understanding of the environmental and molecular interactions that shape the composition of these communities. Although host genetic factors play a role in these interactions, these factors have remained relatively unexplored given the requirement for large population-based cohorts in which both genotyping and microbiome characterization have been performed. We performed whole-genome sequencing of 298 donors from the Human Microbiome Project (HMP) healthy cohort study to accompany existing deep characterization of their microbiomes at various body sites. This analysis yielded an average sequencing depth of 32x, with which we identified 27 million (M) single nucleotide variants and 2.3 M insertions-deletions. Taxonomic composition and functional potential of the microbiome covaried significantly with genetic principal components in the gastrointestinal tract and oral communities, but not in the nares or vaginal microbiota. Example associations included validation of known associations between FUT2 secretor status, as well as a variant conferring hypolactasia near the LCT gene, with Bifidobacterium longum abundance in stool. The associations of microbial features with both high-level genetic attributes and single variants were specific to particular body sites, highlighting the opportunity to find unique genetic mechanisms controlling microbiome properties in the microbial communities from multiple body sites. This study adds deep sequencing of host genomes to the body-wide microbiome sequences already extant from the HMP healthy cohort, creating a unique, versatile, and well-controlled reference for future studies seeking to identify host genetic modulators of the microbiome. The online version of this article (10.1186/s13073-018-0515-8) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
14.9
作者：
Caspi R;Billington R;Ferrer L;Foerster H;Fulcher CA;Keseler IM;Kothari A;Krummenacker M;Latendresse M;Mueller LA;Ong Q;Paley S;Subhraveti P;Weaver DS;Karp PD
通讯作者：
Karp PD
影响因子：
9.2
作者：
Chang CC;Chow CC;Tellier LC;Vattikuti S;Purcell SM;Lee JJ
通讯作者：
Lee JJ
影响因子：
30.8
作者：
Enattah, NS;Sahi, T;Järvelä, I
通讯作者：
Järvelä, I
影响因子：
30.8
作者：
Francioli, Laurent C.;Menelaou, Andronild;Wijmenga, Cisca
通讯作者：
Wijmenga, Cisca