학술논문
Genome-wide association analysis identifies variation in vitamin D receptor and other host factors influencing the gut microbiota
Document Type
Report
Author
Wang, Jun; Thingholm, Louise B; Skiecevi[c caron]ien[e dot], 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
Source
Nature Genetics. November 2016, Vol. 48 Issue 11, p1396, 11 p.
Subject
Language
English
ISSN
1061-4036
Abstract
Author(s): Jun Wang [1, 2]; Louise B Thingholm [3]; Jurgita Skiecevi[c caron]ien[e dot] [3]; Philipp Rausch [1, 2]; Martin Kummen [4, 5, 6, 7]; Johannes R Hov [4, 5, 6, [...]
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[sup.-/-] 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 [less than] 5 x 10[sup.-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.
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[sup.-/-] 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 [less than] 5 x 10[sup.-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.