title: Genome-wide association analysis identifies variation in vitamin D receptor and other host factors influencing the gut microbiota.
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 × 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.
authors.affiliation: Evolutionary Genomics, Max Planck Institute for Evolutionary Biology, Plön, Germany.|Institute for Experimental Medicine, Christian Albrechts University of Kiel, Kiel, Germany.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Institute of Clinical Molecular Biology, Christian Albrechts University of Kiel, Kiel, Germany.
authors.forename: Louise B
authors.initials: LB
authors.lastname: Thingholm
authors.affiliation: Institute of Clinical Molecular Biology, Christian Albrechts University of Kiel, Kiel, Germany.
authors.forename: Jurgita
authors.initials: J
authors.lastname: Skiecevičienė
authors.affiliation: Evolutionary Genomics, Max Planck Institute for Evolutionary Biology, Plön, Germany.|Institute for Experimental Medicine, Christian Albrechts University of Kiel, Kiel, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Rausch
authors.affiliation: Norwegian PSC Research Center, Division of Surgery, Inflammatory Medicine and Transplantation, Oslo, Norway.|Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.|K.G. Jebsen Inflammation Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Martin
authors.initials: M
authors.lastname: Kummen
authors.affiliation: Norwegian PSC Research Center, Division of Surgery, Inflammatory Medicine and Transplantation, Oslo, Norway.|Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.|K.G. Jebsen Inflammation Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.|Section of Gastroenterology, Department of Transplantation Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Johannes R
authors.initials: JR
authors.lastname: Hov
authors.affiliation: Institute of Clinical Molecular Biology, Christian Albrechts University of Kiel, Kiel, Germany.
authors.forename: Frauke
authors.initials: F
authors.lastname: Degenhardt
authors.affiliation: Institute of Clinical Molecular Biology, Christian Albrechts University of Kiel, Kiel, Germany.
authors.forename: Femke-Anouska
authors.identifier: 0000-0003-3652-6402
authors.initials: FA
authors.lastname: Heinsen
authors.affiliation: Institute of Clinical Molecular Biology, Christian Albrechts University of Kiel, Kiel, Germany.
authors.forename: Malte C
authors.identifier: 0000-0002-0685-0052
authors.initials: MC
authors.lastname: Rühlemann
authors.affiliation: Institute of Clinical Molecular Biology, Christian Albrechts University of Kiel, Kiel, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Szymczak
authors.affiliation: Norwegian PSC Research Center, Division of Surgery, Inflammatory Medicine and Transplantation, Oslo, Norway.|Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.|K.G. Jebsen Inflammation Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Kristian
authors.initials: K
authors.lastname: Holm
authors.affiliation: Estonian Genome Center, University of Tartu, Tartu, Estonia.
authors.forename: Tönu
authors.identifier: 0000-0003-1982-6569
authors.initials: T
authors.lastname: Esko
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA.
authors.forename: Jun
authors.identifier: 0000-0001-7465-3133
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Nutrition and Food Sciences, Nutritional Epidemiology, University of Bonn, Bonn, Germany.
authors.forename: Mihaela
authors.initials: M
authors.lastname: Pricop-Jeckstadt
authors.affiliation: Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Samer
authors.initials: S
authors.lastname: Al-Dury
authors.affiliation: Department of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: Pavol
authors.initials: P
authors.lastname: Bohov
authors.affiliation: Institute of Clinical Molecular Biology, Christian Albrechts University of Kiel, Kiel, Germany.
authors.forename: Jörn
authors.identifier: 0000-0002-6919-2595
authors.initials: J
authors.lastname: Bethune
authors.affiliation: Institute of Clinical Molecular Biology, Christian Albrechts University of Kiel, Kiel, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Sommer
authors.affiliation: Institute of Clinical Molecular Biology, Christian Albrechts University of Kiel, Kiel, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Ellinghaus
authors.affiliation: Department of Clinical Science, University of Bergen, Bergen, Norway.|Department of Heart Disease, Haukeland University Hospital, Bergen, Norway.
authors.forename: Rolf K
authors.initials: RK
authors.lastname: Berge
authors.affiliation: Institute of Clinical Molecular Biology, Christian Albrechts University of Kiel, Kiel, Germany.
authors.forename: Matthias
authors.identifier: 0000-0002-5956-3006
authors.initials: M
authors.lastname: Hübenthal
authors.affiliation: Institute of Epidemiology, Christian Albrechts University of Kiel, Kiel, Germany.
authors.forename: Manja
authors.initials: M
authors.lastname: Koch
authors.affiliation: Institute of Human Nutrition and Food Science, University of Kiel, Kiel, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Schwarz
authors.affiliation: Institute of Human Nutrition and Food Science, University of Kiel, Kiel, Germany.
authors.forename: Gerald
authors.initials: G
authors.lastname: Rimbach
authors.affiliation: Institute of Human Nutrition and Food Science, University of Kiel, Kiel, Germany.
authors.forename: Patricia
authors.initials: P
authors.lastname: Hübbe
authors.affiliation: Institute of Clinical Molecular Biology, Christian Albrechts University of Kiel, Kiel, Germany.
authors.forename: Wei-Hung
authors.initials: WH
authors.lastname: Pan
authors.affiliation: Institute of Clinical Molecular Biology, Christian Albrechts University of Kiel, Kiel, Germany.
authors.forename: Raheleh
authors.initials: R
authors.lastname: Sheibani-Tezerji
authors.affiliation: Institute of Clinical Molecular Biology, Christian Albrechts University of Kiel, Kiel, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Häsler
authors.affiliation: Institute of Clinical Molecular Biology, Christian Albrechts University of Kiel, Kiel, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Rosenstiel
authors.affiliation: BioDonostia Health Research Institute, San Sebastian and Ikerbasque, Basque Foundation for Science, Bilbao, Spain.|Unit of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Mauro
authors.initials: M
authors.lastname: D'Amato
authors.affiliation: Institute for Experimental Medicine, Christian Albrechts University of Kiel, Kiel, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Cloppenborg-Schmidt
authors.affiliation: Evolutionary Genomics, Max Planck Institute for Evolutionary Biology, Plön, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Künzel
authors.affiliation: Department of Internal Medicine I, University Hospital S.-H. (UKSH, Campus Kiel), Kiel, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Laudes
authors.affiliation: Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Hanns-Ulrich
authors.initials: HU
authors.lastname: Marschall
authors.affiliation: Institute of Epidemiology, Christian Albrechts University of Kiel, Kiel, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Lieb
authors.affiliation: Department of Nutrition and Food Sciences, Nutritional Epidemiology, University of Bonn, Bonn, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Nöthlings
authors.affiliation: Norwegian PSC Research Center, Division of Surgery, Inflammatory Medicine and Transplantation, Oslo, Norway.|Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.|K.G. Jebsen Inflammation Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.|Section of Gastroenterology, Department of Transplantation Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.|Department of Clinical Medicine, University of Bergen, Bergen, Norway.
authors.forename: Tom H
authors.initials: TH
authors.lastname: Karlsen
authors.affiliation: Evolutionary Genomics, Max Planck Institute for Evolutionary Biology, Plön, Germany.|Institute for Experimental Medicine, Christian Albrechts University of Kiel, Kiel, Germany.
authors.forename: John F
authors.initials: JF
authors.lastname: Baines
authors.affiliation: Institute of Clinical Molecular Biology, Christian Albrechts University of Kiel, Kiel, Germany.
authors.forename: Andre
authors.initials: A
authors.lastname: Franke
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001419:Bacteria / Q000145:classification / Q000235:genetics; D015331:Cohort Studies; D004032:Diet; D005260:Female; D000069196:Gastrointestinal Microbiome; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018167:Receptors, Calcitriol / Q000235:genetics*
chemical_list: D018167:Receptors, Calcitriol; C579457:VDR protein, human