Sharma Arunabh, Junge Olaf, Szymczak Silke, Rühlemann Malte Christoph, Enderle Janna, Schreiber Stefan, Laudes Matthias, Franke Andre, Lieb Wolfgang, Krawczak Michael, Dempfle Astrid
Institute of Medical Informatics and Statistics, Kiel University, Kiel, Germany.
Institute of Medical Biometry and Statistics, University of Lübeck, Lübeck, Germany.
Front Genet. 2023 Jan 23;14:1048312. doi: 10.3389/fgene.2023.1048312. eCollection 2023.
Inflammatory bowel disease (IBD) is characterized by a dysbiosis of the gut microbiome that results from the interaction of the constituting taxa with one another, and with the host. At the same time, host genetic variation is associated with both IBD risk and microbiome composition. In the present study, we defined quantitative traits (QTs) from modules identified in microbial co-occurrence networks to measure the inter-individual consistency of microbial abundance and subjected these QTs to a genome-wide quantitative trait locus (QTL) linkage analysis. Four microbial network modules were consistently identified in two cohorts of healthy individuals, but three of the corresponding QTs differed significantly between IBD patients and unaffected individuals. The QTL linkage analysis was performed in a sub-sample of the Kiel IBD family cohort (IBD-KC), an ongoing study of 256 German families comprising 455 IBD patients and 575 first- and second-degree, non-affected relatives. The analysis revealed five chromosomal regions linked to one of three microbial module QTs, namely on chromosomes 3 (spanning 10.79 cM) and 11 (6.69 cM) for the first module, chr9 (0.13 cM) and chr16 (1.20 cM) for the second module, and chr13 (19.98 cM) for the third module. None of these loci have been implicated in a microbial phenotype before. Our study illustrates the benefit of combining network and family-based linkage analysis to identify novel genetic drivers of microbiome composition in a specific disease context.
炎症性肠病（IBD）的特征是肠道微生物群失调，这是由构成菌群之间以及与宿主之间的相互作用导致的。同时，宿主基因变异与IBD风险和微生物群组成均相关。在本研究中，我们从微生物共现网络中识别出的模块定义了数量性状（QTs），以测量微生物丰度的个体间一致性，并对这些QTs进行全基因组数量性状位点（QTL）连锁分析。在两组健康个体中一致识别出四个微生物网络模块，但IBD患者和未受影响个体之间相应的三个QTs存在显著差异。QTL连锁分析在基尔IBD家系队列（IBD-KC）的一个子样本中进行，IBD-KC是一项正在进行的对256个德国家庭的研究，包括455名IBD患者和575名一级和二级未受影响亲属。分析揭示了与三个微生物模块QTs之一相关的五个染色体区域，即第一个模块位于3号染色体（跨度10.79 cM）和11号染色体（6.69 cM）上，第二个模块位于9号染色体（0.13 cM）和16号染色体（1.20 cM）上，第三个模块位于13号染色体（19.98 cM）上。这些位点以前均未与微生物表型相关联。我们的研究说明了结合网络和基于家系的连锁分析在特定疾病背景下识别微生物群组成新遗传驱动因素的益处。
