Identification of microbiome-host genetics associations using full-length 16S rRNA gene sequencing

人体肠道微生物（微生物组）的收集受到多种因素的影响。此外，在多项研究中，人类遗传学也被确定为一个影响因素。我们提出的项目旨在确定人类遗传变异与肠道微生物之间的联系。为此，我们计划在PacBio测序设备上使用全长16S rRNA基因测序来评估9000名德国人肠道原核生物群落的组成。与目前广泛使用的较短片段illumina测序相比，对微生物16S rRNA基因的全序列测序使我们能够获得更高分辨率的微生物群落组成表征。通过创建微生物共丰度网络和论文与个体宿主表型的相关性，我们希望研究宿主因子和微生物组之间的联系。该项目的核心是开展微生物组与宿主遗传变异之间的全基因组关联研究（GWAS），以评估宿主基因组区域与肠道微生物群落之间的联系。最后，基于这些结果，我们将执行所谓的孟德尔随机化（MR）来评估微生物组与慢性炎症性疾病之间可能的因果关系。

The collection of microorganisms in the human gut (microbiome) is influnced by a multitude of factors. Also human genetics was identified in multiple studies to be an influencing factor. Our proposed Project aims to identify connections between human genetic variants and microorganisms in the gut. For this, we plan to assess the composition of the intestinal prokaryotic community in 9,000 German individuals using full-length 16S rRNA gene sequencing on the PacBio sequencing device.Sequencing of the full 16S rRNA gene of microorganism enables us to obtain a higher resolution representation of the community composition of the microbiome compared to the currently widely performed Illumina-sequencing of shorter fragments.Through the creation of microbial co-abundance networks and the correlation of theses with individual host phenotypes we want to investigate connections between host factors and the microbiome. Central to the project is the performance of genome-wide assocaition studies (GWAS) between microbiome and host-genetic variants to assess connections between host-genomic areas and the microbial community of the gut. Finally, based on these results we will perform so-called Mendelian randomization (MR) to assess possible causal relations between microbiome and for example chronic inflammatory disorders.