Microbiome GWAS（M-GWAS）

Pioneered by mice QTLs and human twins’ studies, genetic influences on the gut microbiome is increasingly recognized. 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, confirming the ~10% genetic contribution to the gut microbiota estimated from European individuals. Using single variants, gene-based and CNV association analysis, we identified numerous/abundant signals associated with gut microbiome. The majority of associations lie in metabolic, neurological and immunological functions, which is particular interesting considering the rapid changes in lifestyle and environmental factors in China and the rising disease incidences. For example, a good portion of our Chinese cohort still harbor Prevotella instead of Bacteroides, similar to other developing countries; and we identified heritability and specific loci for Prevotella species. Other features, such as branched-chain amino acids, might also relate to diabetes risk. Moreover, stratification according to gender led to the identification of differential associations in males and females that were masked when analyzing both genders together, implying sculpturing of an individual’s gut microbiome during infancy or in utero. Our results demonstrate that M-GWAS (Microbiome genome-wide association studies) helps elucidate host–microbe interactions to gain better insight into human health and diseases.