Wang, J., Thingholm, L. B., Skieceviciene, J., Rausch, P., Kummen, M., Hov, J. R., Degenhardt, F., Heinsen, F. A., Ruhlemann, M. C., Szymczak, S., Holm, K., Esko, T., Sun, J., Pricop-Jeckstadt, M., Al-Dury, S., Bohov, P., Bethune, J., Sommer, F., Ellinghaus, D., Berge, R. K., Hubenthal, M., Koch, M., Schwarz, K., Rimbach, Gerald, Hubbe, P., Pan, W. H., Sheibani-Tezerji, R., Hasler, R., Rosenstiel, Philip, D'Amato, M., Cloppenborg-Schmidt, K., Kunzel, S., Laudes, M., Marschall, H. U., Lieb, W., Nothlings, U., Karlsen, T. H., Baines, J. F. and Franke, A. (2016) Genome-wide association analysis identifies variation in vitamin D receptor and other host factors influencing the gut microbiota. Nature Genetics, 48 (11). pp. 1396-1406. DOI 10.1038/ng.3695.

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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 x 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.

Document Type:	Article
Additional Information:	Times Cited: 2 Wang, Jun Thingholm, Louise B. Skieceviciene, Jurgita Rausch, Philipp Kummen, Martin Hov, Johannes R. Degenhardt, Frauke Heinsen, Femke-Anouska Ruehlemann, Malte C. Szymczak, Silke Holm, Kristian Esko, Tonu Sun, Jun Pricop-Jeckstadt, Mihaela Al-Dury, Samer Bohov, Pavol Bethune, Joern Sommer, Felix Ellinghaus, David Berge, Rolf K. Huebenthal, Matthias Koch, Manja Schwarz, Karin Rimbach, Gerald Huebbe, Patricia Pan, Wei-Hung Sheibani-Tezerji, Raheleh Haesler, Robert Rosenstiel, Philipp D'Amato, Mauro Cloppenborg-Schmidt, Katja Kuenzel, Sven Laudes, Matthias Marschall, Hanns-Ulrich Lieb, Wolfgang Noethlings, Ute Karlsen, Tom H. Baines, John F. Franke, Andre
Research affiliation:	Kiel University Kiel University > Kiel Marine Science OceanRep > The Future Ocean - Cluster of Excellence
Refereed:	Yes
Open Access Journal?:	No
Publisher:	Nature Research
Projects:	Future Ocean
Date Deposited:	01 Mar 2017 08:54
Last Modified:	23 Sep 2019 23:05
URI:	https://oceanrep.geomar.de/id/eprint/36365

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