Evidence map›Paper›PMID 27492617›Full record

ArticleGastroenterology2016

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

Dalin Li, Jean-Paul Achkar, Talin Haritunians, Jonathan P Jacobs, Ken Y Hui, Mauro D'Amato, Stephan Brand, Graham Radford-Smith, Jonas Halfvarson, Jan-Hendrik Niess and 30 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Gastroenterology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
84citing papers in PubMed, 1 pooled it
15.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

84 citing papers in PubMed, 1 synthesis or guideline pooled it, 149 citations in OpenAlex.

  1. Pooled it
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24 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

40 authors at 20 institutions in 7 countries.

Dalin LiF. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California.
Jean-Paul AchkarDepartment of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, Ohio.
Talin HarituniansF. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California.
Jonathan P JacobsDivision of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California.
Ken Y HuiDivision of Gastroenterology, Department of Medicine, Yale University, New Haven, Connecticut.
Mauro D'AmatoDepartment of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden; Biocruces Health Research Institute, Barakaldo, Bizkaia, Spain.
Stephan BrandDepartment of Medicine II, University Hospital Munich-Grosshadern, Munich, Germany.
Graham Radford-SmithInflammatory 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.
Jonas HalfvarsonDepartment of Gastroenterology, Faculty of Medicine and Health, Örebro University, Orebro, Sweden.
Jan-Hendrik NiessDepartment 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, Basel, Switzerland.
Subra KugathasanDepartment of Pediatrics, Emory University School of Medicine and Children's Health Care of Atlanta, Atlanta, Georgia.
Carsten BüningInternal Medicine, Krankenhaus Waldfriede, Berlin, Germany.
L Philip SchummDepartment of Public Health Sciences, Biostatistical Laboratory, University of Chicago, Chicago, Illinois.
Lambertus KleiDepartment of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
Ashwin AnanthakrishnanGastroenterology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
Guy AumaisUniversité de Montréal, Montréal, Québec, Canada; Hopital Maisonneuve Rosemont, Montréal, Québec, Canada.
Leonard BaidooDivision of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
Marla DubinskyF. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California; Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, New York.
Claudio FiocchiPathobiology Department, Cleveland Clinic, Cleveland, Ohio.
Jürgen GlasDepartment of Preventive Dentistry and Periodontology, Ludwig-Maximilians-University, Munich, Germany.
Raquel MilgromZane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
Deborah D ProctorDivision of Gastroenterology, Department of Medicine, Yale University, New Haven, Connecticut.
Miguel RegueiroDivision of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
Lisa A SimmsInflammatory Bowel Diseases, Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Joanne M StempakZane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
Stephan R TarganF. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California.
Leif TörkvistDepartment of Clinical Science Intervention and Technology, Karolinska Institutet, Stockholm, Sweden; Center for Digestive Disease, IBD-unit, Karolinska University Hospital, Stockholm, Sweden.
Yashoda SharmaDepartment of Genetic & Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
Bernie DevlinDepartment of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania.
James BornemanDepartment of Plant Pathology and Microbiology, University of California, Riverside, Riverside, California.
Hakon HakonarsonCenter for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Ramnik J XavierGastroenterology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Broad Institute of MIT and Harvard, Cambridge, Massachusetts.
Mark DalyBroad Institute of MIT and Harvard, Cambridge, Massachusetts; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
Steven R BrantDivision of Gastroenterology and Hepatology, School of Medicine, Johns Hopkins University, Baltimore, Maryland; Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland.
John D RiouxUniversité de Montréal, Montréal, Québec, Canada; Montreal Heart Institute, Montréal, Québec, Canada.
Mark S SilverbergZane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
Judy H ChoDepartment of Genetic & Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York; Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
Jonathan BraunPathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California.
Dermot P B McGovernF. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California.
Richard H DuerrDivision of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania. Electronic address: duerr@pitt.edu.
Cedars-Sinai Medical Center · USUniversity of Pittsburgh · USMount Sinai Hospital · CABroad Institute · USCleveland Clinic · USIcahn School of Medicine at Mount Sinai · USUniversity of California, Los Angeles · USYale University · USChicago Department of Public Health · USChildren's Hospital of Philadelphia · USEmory University · USHarvard University · USHôpital Maisonneuve-Rosemont · CAJohns Hopkins University · USKarolinska Institutet · SEKarolinska University Hospital · SEKrankenhaus Waldfriede · DELMU Klinikum · DELudwig-Maximilians-Universität München · DEMontreal Heart Institute · CA

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5M
Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0M
TREATMENT OF DEPRESSION IN ALZHEIMER'S DISEASEP50AG005133 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KAMBOH, M. ILYAS · 1985 to 2019
$43.0M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007205 · NIGMS · YALE UNIVERSITY · PI KAZMIERCZAK, BARBARA I · 1985 to 2019
$42.9M
Virology CoreP30AI028697 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KITCHEN, SCOTT G · 1991 to 2018
$39.9M
Pilot & Feasibility ProgramP30DK043351 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI RAYMOND T CHUNG · 1991 to 2026
$35.3M
Using polygenic scores to enhance both variant discovery, and understanding of functional consequences of genetic variation in IBD.P01DK046763 · NIDDK · CEDARS-SINAI MEDICAL CENTER · PI TARGAN, STEPHAN R. · 1992 to 2020
$31.1M
Mild Cognitive Impairment: A Prospective Community StudyR01AG023651 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI GANGULI, MARY · 2005 to 2020
$27.1M
Pilot and Feasibility ProgramP30DK041301 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ROZENGURT, JUAN ENRIQUE · 1990 to 2019
$18.0M
Inflammatory Bowel Disease Genetics Consortium Data Coordinating CenterU01DK062429 · NIDDK · YALE UNIVERSITY · PI CHO, JUDY H. · 2002 to 2016
$16.8M
The Cleveland Digestive Diseases Research Core Center (DDRCC)P30DK097948 · NIDDK · CASE WESTERN RESERVE UNIVERSITY · PI AMITABH CHAK · 2015 to 2026
$15.6M
AHRQ HHS R01 HS021747NCATS NIH HHS UL1 TR000124NCATS NIH HHS UL1 TR001863NCI NIH HHS P30 CA016042NCI NIH HHS R01 CA141743NIAID NIH HHS P30 AI028697NIAID NIH HHS U01 AI067068NIA NIH HHS P50 AG005133NIA NIH HHS R01 AG023651NIA NIH HHS R01 AG030653NIA NIH HHS R01 AG041718NIDCR NIH HHS U54 DE023798NIDDK NIH HHS F30 DK098927NIDDK NIH HHS P01 DK046763NIDDK NIH HHS P30 DK041301NIDDK NIH HHS P30 DK043351NIDDK NIH HHS P30 DK089502NIDDK NIH HHS P30 DK097948NIDDK NIH HHS R01 DK061451NIDDK NIH HHS R01 DK087694NIDDK NIH HHS R01 DK092235NIDDK NIH HHS R01 DK098231NIDDK NIH HHS T32 DK007180NIDDK NIH HHS U01 DK062413NIDDK NIH HHS U01 DK062420NIDDK NIH HHS U01 DK062422NIDDK NIH HHS U01 DK062423NIDDK NIH HHS U01 DK062429NIDDK NIH HHS U01 DK062431NIDDK NIH HHS U01 DK062432NIGMS NIH HHS T32 GM007205
6 · The paper itself

Abstract

BACKGROUND &

aimsGenome-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).

methodsGenotyping 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.

resultsWe 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)).

conclusionsOur results suggest that an SLC39A8-dependent shift in the gut microbiome could explain its pleiotropic effects on multiple complex diseases including CD.

Indexed as

Mutation, MissenseAllelesCase-Control StudiesCation Transport ProteinsColitis, UlcerativeCrohn DiseaseFemaleGastrointestinal MicrobiomeGenetic PleiotropyGenotypeHumansMaleRisk FactorsCation Transport ProteinsSLC39A8 protein, humanGeneticsInflammatory Bowel DiseasesMicrobiota

Identifiers

PMID27492617
PMCPMC5037008
OpenAlexW2504926893

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.