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

• Published in: Nature genetics Vol. 48; no. 11; pp. 1396 - 1406
• Main Authors: Wang, Jun, Thingholm, Louise B, Skiecevičienė, 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
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.11.2016; Nature Publishing Group
• Subjects: 45/43; 631/208/205/2138; 631/326/325; acid; Adult; Age; Aged; Aged, 80 and over; Agriculture; Animal Genetics and Genomics; Animals; Bacteria - classification; Bacteria - genetics; Biomedicine; Body mass index; Cancer Research; Cell and Molecular Biology; Cell- och molekylärbiologi; Cohort Studies; Diet; disease; expression; Female; Food; Gastrointestinal Microbiome; gene; Gene Function; Gene loci; Genetic aspects; Genetic factors; Genetic variation; Genetics & Heredity; Genome-wide association studies; Genome-Wide Association Study; Genomes; Health aspects; Human Genetics; Humans; Identification and classification; inflammation; Male; Medical Genetics; Medicin och hälsovetenskap; Medicinsk genetik; metabolism; Metabolites; Methods; Mice; Mice, Knockout; Microbiota (Symbiotic organisms); Middle Aged; Polymorphism, Single Nucleotide; population; Receptors, Calcitriol - genetics; shape; Studies; susceptibility; Vitamin D
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/ng.3695

Andre Franke and colleagues perform a genome-wide association study for the gut microbiome, examining the influence of host genetics on overall microbial variation and individual taxa. They find significant associations at the VDR (vitamin D receptor) locus and observe correlations between microbiota and metabolites of VDR, including bile acids. 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.