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 more than 20% genetic contribution to the gut microbiota. Using common variants-, rare variants- and copy number variations (CNVs)-based association analyses, we identified abundant genome-microbiome association especially in metabolic, neurological and immunological functions. The enterotype may have a genetic attribute, with the top 2 loci explaining 11% of the Prevotella-Bacteroides variances. Gender stratification led to the identification of differential associations between sexes. Genetically encoded responses to ectopic presence of oral bacteria in the gut appear to be a common theme in MWAS studies. Our M-GWAS (Microbiome genome-wide association studies) unequivocally illustrates that neither microbiome nor GWAS studies could overlook one another in our quest for a better understanding of human health and diseases.
Keywords: whole genome, metagenome, gut microbiome, M-GWAS, gender stratification
Liu, Xiaomin and Tang, Shanmei and Zhong, Huanzi and Tong, Xin and Jie, Zhuye and Ding, Qiuxia and Wang, Dan and Guo, Ruidong and Xiao, Liang and Xu, Xun and Yang, Huanming and Wang, Jian and Zong, Yang and Liu, Xiao and Zhang, Yong and Brix, Susanne and Kristiansen, Karsten and Hou, Yong and Jia, Huijue and Zhang, Tao, M-GWAS for the Gut Microbiome in Chinese Adults Illuminates on Complex Diseases (May 7, 2019). Available at SSRN: https://ssrn.com/abstract=3383800 or http://dx.doi.org/10.2139/ssrn.3383800
This is a paper under consideration at Cell Press and has not been peer-reviewed.
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