title: Genetic Determinants of the Gut Microbiome in UK Twins.
abstract: Studies in mice and humans have revealed intriguing associations between host genetics and the microbiome. Here we report a 16S rRNA-based analysis of the gut microbiome in 1,126 twin pairs, a subset of which was previously reported. Tripling the sample narrowed the confidence intervals around heritability estimates and uncovered additional heritable taxa, some 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 locus and identify an association between the host gene ALDH1L1 and the bacteria 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.
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14850, USA.
authors.forename: Julia K
authors.initials: JK
authors.lastname: Goodrich
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14850, USA.
authors.forename: Emily R
authors.initials: ER
authors.lastname: Davenport
authors.affiliation: Department of Twin Research & Genetic Epidemiology, King's College London, London SE1 7EH, UK.
authors.forename: Michelle
authors.initials: M
authors.lastname: Beaumont
authors.affiliation: Department of Twin Research & Genetic Epidemiology, King's College London, London SE1 7EH, UK.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Jackson
authors.affiliation: Departments of Pediatrics and Computer Science and Engineering, University of California San Diego, La Jolla, CA 92093, USA.
authors.forename: Rob
authors.initials: R
authors.lastname: Knight
authors.affiliation: Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Carole
authors.initials: C
authors.lastname: Ober
authors.affiliation: Department of Twin Research & Genetic Epidemiology, King's College London, London SE1 7EH, UK.
authors.forename: Tim D
authors.initials: TD
authors.lastname: Spector
authors.affiliation: Department of Twin Research & Genetic Epidemiology, King's College London, London SE1 7EH, UK.
authors.forename: Jordana T
authors.initials: JT
authors.lastname: Bell
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14850, USA.
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Clark
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14850, USA; Department of Microbiome Science, Max Planck Institute for Developmental Biology, 72076 Tübingen, Germany. Electronic address: rel222@cornell.edu.
authors.forename: Ruth E
authors.initials: RE
authors.lastname: Ley
mesh_terms: D001483:Base Sequence; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000235:genetics*; D014644:Genetic Variation; D006801:Humans; D008297:Male; D059013:Microbial Consortia / Q000235:genetics*; D014427:Twins; D006113:United Kingdom