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

Jun Wang, Louise B. Thingholm, Jurgita Skiecevičie, Philipp Rausch, Martin Kummen, Johannes R. Hov, Frauke Degenhardt, Femke Anouska Heinsen, Malte C. Rühlemann, Silke Szymczak, Kristian Holm, Tönu Esko, Jun Sun, Mihaela Pricop-Jeckstadt, Samer Al-Dury, Pavol Bohov, Jörn Bethune, Felix Sommer, David Ellinghaus, Rolf K. BergeMatthias Hübenthal, Manja Koch, Karin Schwarz, Gerald Rimbach, Patricia Hübbe, Wei Hung Pan, Raheleh Sheibani-Tezerji, Robert Häsler, Philipp Rosenstiel, Mauro D'Amato, Katja Cloppenborg-Schmidt, Sven Künzel, Matthias Laudes, Hanns Ulrich Marschall, Wolfgang Lieb, Ute Nöthlings, Tom H. Karlsen, John F. Baines, Andre Franke

Research output: Contribution to journalArticleResearchpeer-review

170 Citations (Scopus)

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 â '/â ' 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 â '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.

Original languageEnglish
Pages (from-to)1396-1406
Number of pages11
JournalNature Genetics
Volume48
Issue number11
DOIs
Publication statusPublished - 1 Nov 2016
Externally publishedYes

Cite this

Wang, J., Thingholm, L. B., Skiecevičie, J., Rausch, P., Kummen, M., Hov, J. R., ... 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), 1396-1406. https://doi.org/10.1038/ng.3695
Wang, Jun ; Thingholm, Louise B. ; Skiecevičie, Jurgita ; Rausch, Philipp ; Kummen, Martin ; Hov, Johannes R. ; Degenhardt, Frauke ; Heinsen, Femke Anouska ; Rühlemann, Malte C. ; Szymczak, Silke ; Holm, Kristian ; Esko, Tönu ; Sun, Jun ; Pricop-Jeckstadt, Mihaela ; Al-Dury, Samer ; Bohov, Pavol ; Bethune, Jörn ; Sommer, Felix ; Ellinghaus, David ; Berge, Rolf K. ; Hübenthal, Matthias ; Koch, Manja ; Schwarz, Karin ; Rimbach, Gerald ; Hübbe, Patricia ; Pan, Wei Hung ; Sheibani-Tezerji, Raheleh ; Häsler, Robert ; Rosenstiel, Philipp ; D'Amato, Mauro ; Cloppenborg-Schmidt, Katja ; Künzel, Sven ; Laudes, Matthias ; Marschall, Hanns Ulrich ; Lieb, Wolfgang ; Nöthlings, Ute ; Karlsen, Tom H. ; Baines, John F. ; Franke, Andre. / Genome-wide association analysis identifies variation in Vitamin D receptor and other host factors influencing the gut microbiota. In: Nature Genetics. 2016 ; Vol. 48, No. 11. pp. 1396-1406.
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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 {\^a} '/{\^a} ' 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 {\^a} '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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Wang, J, Thingholm, LB, Skiecevičie, J, Rausch, P, Kummen, M, Hov, JR, Degenhardt, F, Heinsen, FA, Rühlemann, MC, Szymczak, S, Holm, K, Esko, T, Sun, J, Pricop-Jeckstadt, M, Al-Dury, S, Bohov, P, Bethune, J, Sommer, F, Ellinghaus, D, Berge, RK, Hübenthal, M, Koch, M, Schwarz, K, Rimbach, G, Hübbe, P, Pan, WH, Sheibani-Tezerji, R, Häsler, R, Rosenstiel, P, D'Amato, M, Cloppenborg-Schmidt, K, Künzel, S, Laudes, M, Marschall, HU, Lieb, W, Nöthlings, U, Karlsen, TH, Baines, JF & Franke, A 2016, 'Genome-wide association analysis identifies variation in Vitamin D receptor and other host factors influencing the gut microbiota', Nature Genetics, vol. 48, no. 11, pp. 1396-1406. https://doi.org/10.1038/ng.3695

Genome-wide association analysis identifies variation in Vitamin D receptor and other host factors influencing the gut microbiota. / Wang, Jun; Thingholm, Louise B.; Skiecevičie, Jurgita; Rausch, Philipp; Kummen, Martin; Hov, Johannes R.; Degenhardt, Frauke; Heinsen, Femke Anouska; Rühlemann, Malte C.; Szymczak, Silke; Holm, Kristian; Esko, Tönu; Sun, Jun; Pricop-Jeckstadt, Mihaela; Al-Dury, Samer; Bohov, Pavol; Bethune, Jörn; Sommer, Felix; Ellinghaus, David; Berge, Rolf K.; Hübenthal, Matthias; Koch, Manja; Schwarz, Karin; Rimbach, Gerald; Hübbe, Patricia; Pan, Wei Hung; Sheibani-Tezerji, Raheleh; Häsler, Robert; Rosenstiel, Philipp; D'Amato, Mauro; Cloppenborg-Schmidt, Katja; Künzel, Sven; Laudes, Matthias; Marschall, Hanns Ulrich; Lieb, Wolfgang; Nöthlings, Ute; Karlsen, Tom H.; Baines, John F.; Franke, Andre.

In: Nature Genetics, Vol. 48, No. 11, 01.11.2016, p. 1396-1406.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Genome-wide association analysis identifies variation in Vitamin D receptor and other host factors influencing the gut microbiota

AU - Wang, Jun

AU - Thingholm, Louise B.

AU - Skiecevičie, Jurgita

AU - Rausch, Philipp

AU - Kummen, Martin

AU - Hov, Johannes R.

AU - Degenhardt, Frauke

AU - Heinsen, Femke Anouska

AU - Rühlemann, Malte C.

AU - Szymczak, Silke

AU - Holm, Kristian

AU - Esko, Tönu

AU - Sun, Jun

AU - Pricop-Jeckstadt, Mihaela

AU - Al-Dury, Samer

AU - Bohov, Pavol

AU - Bethune, Jörn

AU - Sommer, Felix

AU - Ellinghaus, David

AU - Berge, Rolf K.

AU - Hübenthal, Matthias

AU - Koch, Manja

AU - Schwarz, Karin

AU - Rimbach, Gerald

AU - Hübbe, Patricia

AU - Pan, Wei Hung

AU - Sheibani-Tezerji, Raheleh

AU - Häsler, Robert

AU - Rosenstiel, Philipp

AU - D'Amato, Mauro

AU - Cloppenborg-Schmidt, Katja

AU - Künzel, Sven

AU - Laudes, Matthias

AU - Marschall, Hanns Ulrich

AU - Lieb, Wolfgang

AU - Nöthlings, Ute

AU - Karlsen, Tom H.

AU - Baines, John F.

AU - Franke, Andre

PY - 2016/11/1

Y1 - 2016/11/1

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AB - 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 â '/â ' 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 â '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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DO - 10.1038/ng.3695

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