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

Authors:

Wang J, Thingholm LB, Skieceviciene J, Rausch P, Kummen M, Hov JR, et al.

Year of publication:

2016

Volume:

48

Issue:

11

ISSN:

Journal (long):

Nature Genetics

Journal (short):

Nat. Genet.

Impact factor:

27603

Abstract:

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.

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