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Recent genetic studies in mice and humans have revealed intriguing genetic associations with the gut microbiome. Here we report a 16S rRNA-based analysis of the gut microbiome in 1,126 twin pairs, a subset of which we previously analyzed. Tripling the sample reduced the confidence intervals around heritability estimates and uncovered newly heritable taxa, many of which are validated in other studies. Repeat sampling of subjects showed heritable taxa to be temporally stable. A candidate gene approach uncovered associations between heritable taxa and genes related to diet, metabolism and olfaction. We replicate an association between Bifidobacterium and the lactase (LCT) gene region and identify an association between ALDH1L1 and SHA-98, suggesting a link between formate production and blood pressure. Additional genes detected are involved in barrier defense and self/non-self recognition. Our results indicate that diet sensing, metabolism, and immune defense are important drivers of human-microbiome co-evolution. |