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A Pleiotropic Misse...
A Pleiotropic Missense Variant in SLC39A8 Is Associated With Crohn's Disease and Human Gut Microbiome Composition
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- Li, Dalin (författare)
- F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, USA
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- Achkar, Jean-Paul (författare)
- Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland OH, USA
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- 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
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- Hui, Ken Y. (författare)
- Division of Gastroenterology, Department of Medicine, Yale University, New Haven CT, USA
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- D'Amato, Mauro (författare)
- Karolinska Institutet
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- Brand, Stephan (författare)
- Department of Medicine II, University Hospital Munich-Grosshadern, Munich, Germany
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- 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
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- Halfvarson, Jonas, 1970- (författare)
- Örebro universitet,Institutionen för medicinska vetenskaper,Department of Gastroenterology, Örebro University Hospital, Örebro, Sweden
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- 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
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- Kugathasan, Subra (författare)
- Department of Pediatrics, Emory University School of Medicine and Children's Health Care of Atlanta, Atlanta Ga, USA
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- Büning, Carsten (författare)
- Internal Medicine, Krankenhaus Waldfriede, Berlin, Germany
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- Schumm, L. Philip (författare)
- Department of Public Health Sciences, Biostatistical Laboratory, University of Chicago, Chicago ILL, USA
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- Klei, Lambertus (författare)
- Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh PA, USA
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- Ananthakrishnan, Ashwin (författare)
- Gastroenterology Unit, Massachusetts General Hospital, Harvard Medical School, Boston MA, USA
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- Aumais, Guy (författare)
- Université de Montréal, Montréal QC, Canada; Hopital Maisonneuve Rosemont, Montréal QC, Canada
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- Baidoo, Leonard (författare)
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh PA, USA
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- 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
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- Fiocchi, Claudio (författare)
- Pathobiology Department, Cleveland Clinic, Cleveland OH, USA
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- Glas, Jürgen (författare)
- Department of Preventive Dentistry and Periodontology, Ludwig-Maximilians-University, Munich, Germany
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- Milgrom, Raquel (författare)
- Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada
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- Proctor, Deborah D. (författare)
- Division of Gastroenterology, Department of Medicine, Yale University, New Haven CT, USA
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- Regueiro, Miguel (författare)
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh PA, USA
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- Simms, Lisa A. (författare)
- Inflammatory Bowel Diseases, Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Australia
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- Stempak, Joanne M. (författare)
- Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, University of Toronto, Toronto ON, Canada
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- Targan, Stephan R. (författare)
- F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, USA
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- Törkvist, Leif (författare)
- Karolinska Institutet
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- Sharma, Yashoda (författare)
- Department of Genetic & Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York NY, USA
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- 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
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- Borneman, James (författare)
- Department of Plant Pathology and Microbiology, University of California, Riverside, Riverside CA, USA
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- Hakonarson, Hakon (författare)
- Center for Applied Genomics, The Children’s Hospital of Philadelphia, Philadelphia PA, USA
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- Xavier, Ramnik J. (författare)
- Gastroenterology Unit, Massachusetts General Hospital, Harvard Medical School, Boston , USA; Broad Institute of MIT and Harvard, Cambridge MA, USA
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- 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
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- 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
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- Rioux, John D. (författare)
- Université de Montréal, Montréal QC, Canada; Montreal Heart Institute, Montréal OC, Canada
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- Silverberg, Mark S. (författare)
- Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, University of Toronto, Toronto ON, Canada
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- 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
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- Braun, Jonathan (författare)
- Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles CA, USA;
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- McGovern, Dermot P. B. (författare)
- F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, USA
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- 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.
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Ingår i: Gastroenterology. - : Saunders Elsevier. - 0016-5085 .- 1528-0012. ; 151:4, s. 724-732
- Relaterad länk:
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https://europepmc.or...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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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
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Gastroenterologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Gastroenterology and Hepatology (hsv//eng)
Nyckelord
- Genetics; Inflammatory Bowel Diseases; Microbiota
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- Av författaren/redakt...
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Li, Dalin
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Achkar, Jean-Pau ...
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Haritunians, Tal ...
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Jacobs, Jonathan ...
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Hui, Ken Y.
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D'Amato, Mauro
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visa fler...
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Brand, Stephan
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Radford-Smith, G ...
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Halfvarson, Jona ...
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Niess, Jan-Hendr ...
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Kugathasan, Subr ...
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Büning, Carsten
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Schumm, L. Phili ...
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Klei, Lambertus
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Ananthakrishnan, ...
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Aumais, Guy
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Baidoo, Leonard
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Dubinsky, Marla
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Fiocchi, Claudio
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Glas, Jürgen
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Milgrom, Raquel
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Proctor, Deborah ...
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Regueiro, Miguel
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Simms, Lisa A.
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Stempak, Joanne ...
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Targan, Stephan ...
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Törkvist, Leif
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Sharma, Yashoda
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Devlin, Bernie
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Borneman, James
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Hakonarson, Hako ...
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Xavier, Ramnik J ...
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Daly, Mark
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Brant, Steven R.
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Rioux, John D.
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Silverberg, Mark ...
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Cho, Judy H.
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Braun, Jonathan
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McGovern, Dermot ...
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Duerr, Richard H ...
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- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Gastroenterologi
- Artiklar i publikationen
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Gastroenterology
- Av lärosätet
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Örebro universitet
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Karolinska Institutet