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

TitelGenome-wide association analysis identifies variation in vitamin D receptor and other host factors influencing the gut microbiota.
MedientypJournal Article
Jahr der Veröffentlichung2016
AutorenWang J, Thingholm LB, Skiecevičienė J, Rausch P, Kummen M, Hov JR, Degenhardt F, Heinsen F-A, 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 W-H, Sheibani-Tezerji R, Häsler R, Rosenstiel P, D'Amato M, Cloppenborg-Schmidt K, Künzel S, Laudes M, Marschall H-U, Lieb W, Nöthlings U, Karlsen TH, Baines JF, Franke A
JournalNat Genet
Volume48
Ausgabe11
Pagination1396-1406
Datum der Veröffentlichung2016 11
ISSN1546-1718
SchlüsselwörterAdult, Aged, Aged, 80 and over, Animals, Bacteria, Cohort Studies, Diet, Female, Gastrointestinal Microbiome, Genome-Wide Association Study, Humans, Male, Mice, Mice, Knockout, Middle Aged, Polymorphism, Single Nucleotide, Receptors, Calcitriol
Zusammenfassung

<p>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) 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.</p>

DOI10.1038/ng.3695
Alternate JournalNat. Genet.
PubMed ID27723756
PubMed Central IDPMC5626933
Grant ListR01 DK105118 / DK / NIDDK NIH HHS / United States
R03 DK089010 / DK / NIDDK NIH HHS / United States