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Genome-wide association analysis identifies variation in vitamin D receptor and other host factors influencing the gut microbiota

MPG-Autoren
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Wang,  Jun
Guest Group Evolutionary Genomics, Max Planck Institute for Evolutionary Biology, Max Planck Society;

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Rausch,  Philipp
Guest Group Evolutionary Genomics, Max Planck Institute for Evolutionary Biology, Max Planck Society;

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Künzel,  Sven
Department Evolutionary Genetics, Max Planck Institute for Evolutionary Biology, Max Planck Society;

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Baines,  John F.
Guest Group Evolutionary Genomics, Max Planck Institute for Evolutionary Biology, Max Planck Society;

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Zitation

Wang, J., Thingholm, L. B., Skiecevičienė, J., Rausch, P., Kummen, M., Hov, J. R., et al. (2016). Genome-wide association analysis identifies variation in vitamin D receptor and other host factors influencing the gut microbiota. Nature Genetics, 48, 1396-1406. doi:10.1038/ng.3695.


Zitierlink: http://hdl.handle.net/11858/00-001M-0000-002C-0A0F-F
Zusammenfassung
Human gut microbiota is an important determinant for health and disease, and recent studies emphasize the numerous factors shaping its diversity. Here we performed a genome-wide association study (GWAS) of the gut microbiota using two cohorts from northern Germany totaling 1,812 individuals. Comprehensively controlling for diet and non-genetic parameters, we identify genome-wide significant associations for overall microbial variation and individual taxa at multiple genetic loci, including the VDR gene (encoding vitamin D receptor). We observe significant shifts in the microbiota of Vdr−/− mice relative to control mice and correlations between the microbiota and serum measurements of selected bile and fatty acids in humans, including known ligands and downstream metabolites of VDR. Genome-wide significant (P < 5 × 10−8) associations at multiple additional loci identify other important points of host–microbe intersection, notably several disease susceptibility genes and sterol metabolism pathway components. Non-genetic and genetic factors each account for approximately 10% of the variation in gut microbiota, whereby individual effects are relatively small.