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Sökning: onr:"swepub:oai:DiVA.org:oru-52738" > A Pleiotropic Misse...

A Pleiotropic Missense Variant in SLC39A8 Is Associated With Crohn's Disease and Human Gut Microbiome Composition

Li, Dalin (författare)
F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, USA
Achkar, Jean-Paul (författare)
Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland OH, USA
Haritunians, Talin (författare)
F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, USA
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Jacobs, Jonathan P. (författare)
Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, USA
Hui, Ken Y. (författare)
Division of Gastroenterology, Department of Medicine, Yale University, New Haven CT, USA
D'Amato, Mauro (författare)
Karolinska Institutet
Brand, Stephan (författare)
Department of Medicine II, University Hospital Munich-Grosshadern, Munich, Germany
Radford-Smith, Graham (författare)
Inflammatory Bowel Diseases, Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Australia; Department of Gastroenterology, Royal Brisbane and Women’s Hospital, Brisbane, Australia; School of Medicine, University of Queensland, Brisbane, Australia
Halfvarson, Jonas, 1970- (författare)
Örebro universitet,Institutionen för medicinska vetenskaper,Department of Gastroenterology, Örebro University Hospital, Örebro, Sweden
Niess, Jan-Hendrik (författare)
Department of Internal Medicine I, University of Ulm, Ulm, Germany; Division of Visceral Surgery and Medicine, Department of Gastroenterology, Inselspital Bern, Bern, Switzerland; Gastroenterology and Hepatology, University Hospital, Basel, Switzerland
Kugathasan, Subra (författare)
Department of Pediatrics, Emory University School of Medicine and Children's Health Care of Atlanta, Atlanta Ga, USA
Büning, Carsten (författare)
Internal Medicine, Krankenhaus Waldfriede, Berlin, Germany
Schumm, L. Philip (författare)
Department of Public Health Sciences, Biostatistical Laboratory, University of Chicago, Chicago ILL, USA
Klei, Lambertus (författare)
Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh PA, USA
Ananthakrishnan, Ashwin (författare)
Gastroenterology Unit, Massachusetts General Hospital, Harvard Medical School, Boston MA, USA
Aumais, Guy (författare)
Université de Montréal, Montréal QC, Canada; Hopital Maisonneuve Rosemont, Montréal QC, Canada
Baidoo, Leonard (författare)
Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh PA, USA
Dubinsky, Marla (författare)
F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, USA; Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York NY, USA
Fiocchi, Claudio (författare)
Pathobiology Department, Cleveland Clinic, Cleveland OH, USA
Glas, Jürgen (författare)
Department of Preventive Dentistry and Periodontology, Ludwig-Maximilians-University, Munich, Germany
Milgrom, Raquel (författare)
Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada
Proctor, Deborah D. (författare)
Division of Gastroenterology, Department of Medicine, Yale University, New Haven CT, USA
Regueiro, Miguel (författare)
Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh PA, USA
Simms, Lisa A. (författare)
Inflammatory Bowel Diseases, Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Australia
Stempak, Joanne M. (författare)
Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, University of Toronto, Toronto ON, Canada
Targan, Stephan R. (författare)
F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, USA
Törkvist, Leif (författare)
Karolinska Institutet
Sharma, Yashoda (författare)
Department of Genetic & Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York NY, USA
Devlin, Bernie (författare)
Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh PA, USA; Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh PA, USA
Borneman, James (författare)
Department of Plant Pathology and Microbiology, University of California, Riverside, Riverside CA, USA
Hakonarson, Hakon (författare)
Center for Applied Genomics, The Children’s Hospital of Philadelphia, Philadelphia PA, USA
Xavier, Ramnik J. (författare)
Gastroenterology Unit, Massachusetts General Hospital, Harvard Medical School, Boston , USA; Broad Institute of MIT and Harvard, Cambridge MA, USA
Daly, Mark (författare)
Broad Institute of MIT and Harvard, Cambridge MA, USA; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston MA, USA
Brant, Steven R. (författare)
Division of Gastroenterology and Hepatology, School of Medicine, Johns Hopkins University, Baltimore MD, USA; Bloomberg School of Public Health, Johns Hopkins University, Baltimore MD, USA
Rioux, John D. (författare)
Université de Montréal, Montréal QC, Canada; Montreal Heart Institute, Montréal OC, Canada
Silverberg, Mark S. (författare)
Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, University of Toronto, Toronto ON, Canada
Cho, Judy H. (författare)
Department of Genetic & Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York NY, USA; Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York NY, USA
Braun, Jonathan (författare)
Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles CA, USA;
McGovern, Dermot P. B. (författare)
F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, USA
Duerr, Richard H. (författare)
Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh PA, USA; Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh PA, USA
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F Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, USA Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland OH, USA (creator_code:org_t)
Saunders Elsevier, 2016
2016
Engelska.
Ingår i: Gastroenterology. - : Saunders Elsevier. - 0016-5085 .- 1528-0012. ; 151:4, s. 724-732
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • Background & Aims: Genome-wide association studies have identified 200 inflammatory bowel disease (IBD) loci, but the genetic architecture of Crohn's disease (CD) and ulcerative colitis remain incompletely defined. Here, we aimed to identify novel associations between IBD and functional genetic variants using the Illumina ExomeChip (San Diego, CA).Methods: Genotyping was performed in 10,523 IBD cases and 5726 non-IBD controls. There were 91,713 functional single-nucleotide polymorphism loci in coding regions analyzed. A novel identified association was replicated further in 2 independent cohorts. We further examined the association of the identified single-nucleotide polymorphism with microbiota from 338 mucosal lavage samples in the Mucosal Luminal Interface cohort measured using 16S sequencing.Results: We identified an association between CD and a missense variant encoding alanine or threonine at position 391 in the zinc transporter solute carrier family 39, member 8 protein (SLC39A8 alanine 391 threonine, rs13107325) and replicated the association with CD in 2 replication cohorts (combined meta-analysis P = 5.55 × 10(-13)). This variant has been associated previously with distinct phenotypes including obesity, lipid levels, blood pressure, and schizophrenia. We subsequently determined that the CD risk allele was associated with altered colonic mucosal microbiome composition in both healthy controls (P = .009) and CD cases (P = .0009). Moreover, microbes depleted in healthy carriers strongly overlap with those reduced in CD patients (P = 9.24 × 10(-16)) and overweight individuals (P = 6.73 × 10(-16)).Conclusions: Our results suggest that an SLC39A8-dependent shift in the gut microbiome could explain its pleiotropic effects on multiple complex diseases including CD.

Ämnesord

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Gastroenterology and Hepatology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Gastroenterologi (hsv//swe)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine (hsv//eng)

Nyckelord

Genetics; Inflammatory Bowel Diseases; Microbiota

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