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M-GWAS for the gut microbiome in Chinese adults illuminates on complex diseases

By Xiaomin Liu, Shanmei Tang, Huanzi Zhong, Xin Tong, Zhuye Jie, Qiuxia Ding, Dan Wang, Ruidong Guo, Liang Xiao, Xun Xu, Huanming Yang, Jian Wang, Yang Zong, Xiao Liu, Yong Zhang, Susanne Brix, Karsten Kristiansen, Yong Hou, Huijue Jia, Tao Zhang

Posted 15 Aug 2019
bioRxiv DOI: 10.1101/736413

The gut microbiome has been established as a key environmental factor to health. Genetic influences on the gut microbiome have been reported, yet, doubts remain as to the significance of genetic associations. Here, we provide shotgun data for whole genome and whole metagenome from a Chinese cohort, identifying no less than 20% genetic contribution to the gut microbiota. Using common variants-, rare variants- and copy number variations (CNVs)-based association analyses, we identified abundant signals associated with the gut microbiome especially in metabolic, neurological and immunological functions. The controversial concept of enterotypes may have a genetic attribute, with the top 2 loci explaining 11% of the Prevotella-Bacteroides variances. Stratification according to gender led to the identification of differential associations in males and females. Genetically encoded responses to ectopic presence of oral bacteria in the gut appear to be a common theme in a number of diseases investigated by MWAS (Metagenome-wide association studies). Our two-stage M-GWAS (Microbiome genome-wide association studies) on a total of 1295 individuals unequivocally illustrates that neither microbiome nor GWAS studies could overlook one another in our quest for a better understanding of human health and diseases.

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