ArticleNature genetics2015
High-density mapping of the MHC identifies a shared role for HLA-DRB1*01:03 in inflammatory bowel diseases and heterozygous advantage in ulcerative colitis.
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Article in Nature genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 196 papers, 8 of them syntheses that pooled it.
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196citing papers in PubMed, 8 pooled it
29.9field-weighted citation impact, top 1% of its field
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Who cites it
196 citing papers in PubMed, 8 syntheses or guidelines pooled it, 371 citations in OpenAlex.
- Polygenic risk score for ulcerative colitis predicts immune checkpoint inhibitor-mediated colitis.Nature communications · 2024Pooled it
- Pooled it
- Sex-Dimorphic Analyses Identify Novel and Sex-Specific Genetic Associations in Inflammatory Bowel Disease.Inflammatory bowel diseases · 2023Pooled it
- Classical Human Leukocyte Antigen Alleles and C4 Haplotypes Are Not Significantly Associated With Depression.Biological psychiatry · 2020Pooled it
- Association of rosacea with inflammatory bowel disease: A MOOSE-compliant meta-analysis.Medicine · 2019Pooled it
- Genetic Factors Interact With Tobacco Smoke to Modify Risk for Inflammatory Bowel Disease in Humans and Mice.Gastroenterology · 2017Pooled it
- Genome-Wide Association Study Identifies African-Specific Susceptibility Loci in African Americans With Inflammatory Bowel Disease.Gastroenterology · 2017Pooled it
- Systematic review: genetic biomarkers associated with anti-TNF treatment response in inflammatory bowel diseases.Alimentary pharmacology & therapeutics · 2016Pooled it
- Predicting Toxicity and Response to Pembrolizumab Through Germline Genomic HLA Class 1 Analysis.JNCI cancer spectrum · 2021Trial
- Genetic architecture differences between pediatric and adult-onset inflammatory bowel diseases in the Polish population.Scientific reports · 2016Trial
- Towards Precision Medicine in Inflammatory Bowel Diseases: Pharmacogenetic Predictors of Ustekinumab Effectiveness and Persistence.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Review
- Shared CD4+ T cell receptor specificity groups in Crohn's disease and ulcerative colitis.JCI insight · 2026Article
- Large-scale human genomic resources drive innovations toward forensic intelligent source attribution and precision identification.International journal of legal medicine · 2026Review
- Local and circulating cytotoxic CD4medRxiv : the preprint server for health sciences · 2026Article
- A Comprehensive HLA-DR4 MHC Class II Tetramer Platform for the Detection and Functional Validation of Post-Translational Modification Neoantigens.International journal of molecular sciences · 2026Article
- Article
- Mapping adaptive immune responses toward fungal antigens in inflammatory bowel disease using T cell repertoire sequencing and phage-immunoprecipitation sequencing.Journal of Crohn's & colitis · 2026Article
- Polygenic risk scores for Crohn's disease risk prediction in a Chinese population: insights from multi-ethnic genome-wide association studies.European journal of medical research · 2026Article
- Whole exome sequencing analysis of suicidal thoughts and behaviors in a veteran cohort implicates inflammatory pathways and genes previously associated with psychiatric and neurodegenerative diseases.Journal of affective disorders · 2026Article
136 more citing papers are in PubMed but not listed here.
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Authors and funding
33 authors at 15 institutions in 9 countries.
Philippe GoyetteResearch Center, Montreal Heart Institute, Montreal, Quebec, Canada.
Gabrielle BoucherResearch Center, Montreal Heart Institute, Montreal, Quebec, Canada.
Dermot Mallon1] Department of Surgery, University of Cambridge, Cambridge, UK. [2] National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre, Cambridge, UK.ORCID 0000000174341201
Eva EllinghausInstitute of Clinical Molecular Biology, Christian Albrechts University, Kiel, Germany.ORCID 0000000329143382
Luke Jostins1] Wellcome Trust Centre for Human Genetics, University of Oxford, Headington, UK. [2] Christ Church, University of Oxford, St Aldates, UK.
Hailiang Huang1] Analytic and Translational Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. [2] Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.ORCID 0000000314615762
Stephan Ripke1] Analytic and Translational Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. [2] Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.ORCID 000000033622835X
Elena S Gusareva1] Systems and Modeling Unit, Montefiore Institute, University of Liege, Liege, Belgium. [2] Bioinformatics and Modeling, GIGA-R (Groupe Interdisciplinaire de Génoprotéomique Appliquée) Research Center, University of Liege, Liege, Belgium.
Vito Annese1] Unit of Gastroenterology, IRCCS-CSS (Istituto di Ricovero e Cura a Carattere Scientifico-Casa Sollievo della Sofferenza) Hospital, San Giovanni Rotondo, Italy. [2] Unit of Gastroenterology SOD2 (Strutture Organizzative Dipartimentali), Azienda Ospedaliero Universitaria (AOU) Careggi, Florence, Italy.
Stephen L HauserDepartment of Neurology, University of California, San Francisco, San Francisco, California, USA.
Jorge R OksenbergDepartment of Neurology, University of California, San Francisco, San Francisco, California, USA.
Ingo ThomsenInstitute of Clinical Molecular Biology, Christian Albrechts University, Kiel, Germany.
Stephen Leslie1] Murdoch Children's Research Institute, Parkville, Victoria, Australia. [2] Department of Mathematics and Statistics, University of Melbourne, Melbourne, Victoria, Australia.
International Inflammatory Bowel Disease Genetics Consortium
Australia and New Zealand IBDGC
Belgium IBD Genetics Consortium
Italian Group for IBD Genetic Consortium
NIDDK Inflammatory Bowel Disease Genetics Consortium
United Kingdom IBDGC
Wellcome Trust Case Control Consortium
Quebec IBD Genetics Consortium
Mark J Daly1] Analytic and Translational Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. [2] Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Kristel Van Steen1] Systems and Modeling Unit, Montefiore Institute, University of Liege, Liege, Belgium. [2] Bioinformatics and Modeling, GIGA-R (Groupe Interdisciplinaire de Génoprotéomique Appliquée) Research Center, University of Liege, Liege, Belgium.
Richard H Duerr1] Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. [2] Department of Human Genetics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania, USA.
Jeffrey C BarrettWellcome Trust Sanger Institute, Hinxton, UK.ORCID 000000021152370X
Dermot P B McGovernF. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
L Philip SchummDepartment of Public Health Sciences, University of Chicago, Chicago, Illinois, USA.
James A Traherne1] Cambridge Institute for Medical Research, Cambridge, UK. [2] Department of Pathology, University of Cambridge, Cambridge, UK.
Mary N Carrington1] Cancer and Inflammation Program, Laboratory of Experimental Immunology, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA. [2] Ragon Institute of Massachusetts General Hospital, MIT and Harvard, Cambridge, Massachusetts, USA.
Vasilis Kosmoliaptsis1] Department of Surgery, University of Cambridge, Cambridge, UK. [2] National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre, Cambridge, UK.
Tom H Karlsen1] Research Institute of Internal Medicine, Department of Transplantation Medicine, Division of Cancer, Surgery and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway. [2] Norwegian Primary Sclerosing Cholangitis Research Center, Department of Transplantation Medicine, Division of Cancer, Surgery and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway. [3] K.G. Jebsen Inflammation Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Andre FrankeInstitute of Clinical Molecular Biology, Christian Albrechts University, Kiel, Germany.
John D Rioux1] Research Center, Montreal Heart Institute, Montreal, Quebec, Canada. [2] Faculté de Médecine, Université de Montréal, Montreal, Quebec, Canada.
Broad Institute · USChristian-Albrechts-Universität zu Kiel · DEMontreal Heart Institute · CAUniversity of Cambridge · GBUniversity of California, San Francisco · USUniversity of Liège · BECanterbury Christ Church University · GBCasa Sollievo della Sofferenza · ITCedars-Sinai Medical Center · USChicago Department of Public Health · USLeidos (United States) · USOslo University Hospital · NOThe University of Melbourne · AUUniversity of Pittsburgh · USWellcome Sanger Institute · GB
Funding
University of Pittsburgh Clinical and Translational Science InstituteUL1TR000005 · NCATS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI REIS, STEVEN E · 2012 to 2015
$50.8MPilot & Feasibility ProgramP30DK043351 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI RAYMOND T CHUNG · 1991 to 2026
$35.3MUsing 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
$31.1MEffects of genetic polymorphism in MHC, KIR, and related loci on human diseaseZIABC010791 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI CARRINGTON, MARY N. · 2009 to 2025
$18.2MInflammatory Bowel Disease Genetics Consortium Data Coordinating CenterU01DK062429 · NIDDK · YALE UNIVERSITY · PI CHO, JUDY H. · 2002 to 2016
$16.8MA Haplotype Map for Multiple SclerosisR01NS049477 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HAUSER, STEPHEN L · 2005 to 2014
$15.3MPrecision IBD via genetics and genomics: integrating International and multi-omic datasets, expanding studies in diverse populations, and defining mechanisms of unmet clinical needs in IBDU24DK062429 · NIDDK · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Ling-shiang Chuang, Ron Do · 2017 to 2026
$13.9MUtilizing the Phenomics of IBD to Enhance Gene DiscoveryU01DK062413 · NIDDK · CEDARS-SINAI MEDICAL CENTER · PI Dermot Patrick McGovern · 2002 to 2026
$12.2MThe Role of HLA and KIR in Rheumatoid Arthritis and Crohn's DiseaseU01AI067068 · NIAID · STANFORD UNIVERSITY · PI ERLICH, HENRY A, TRACHTENBERG, ELIZABETH A · 2005 to 2014
$10.9MIBD Gene Mapping by Clinical and Population SubsetsU01DK062431 · NIDDK · RUTGERS BIOMEDICAL AND HEALTH SCIENCES · PI Steven R Brant · 2002 to 2026
$10.7MSystemic Lupus Erythematosus and Ulcerative Colitis StudyU19AI067152 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HAUSER, STEPHEN L · 2005 to 2009
$10.1MUniversite de Montreal IBD Genetics Research CenterU01DK062432 · NIDDK · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI John D. Rioux · 2002 to 2026
$9.6MAHRQ HHS HS021747AHRQ HHS R01 HS021747Chief Scientist Office CZB/4/540Chief Scientist Office ETM/137Chief Scientist Office ETM/75Department of Health NIHR-RP-R3-12-026Medical Research Council G0600329Medical Research Council G0800675MRF_ C0482NCATS NIH HHS UL1 TR000005NCI NIH HHS CA141743NCI NIH HHS R01 CA141743NIAID NIH HHS U01 AI067068NIAID NIH HHS U19 AI067152NIDCR NIH HHS U54 DE023789NIDCR NIH HHS U54 DE023789-01NIDDK NIH HHS P01 DK046763NIDDK NIH HHS P01 DK046763-19NIDDK NIH HHS P30 DK043351NIDDK NIH HHS R01 DK064869NIDDK NIH HHS U01 DK062413NIDDK NIH HHS U01 DK062420NIDDK NIH HHS U01 DK062423NIDDK NIH HHS U01 DK062429NIDDK NIH HHS U01 DK062429-14NIDDK NIH HHS U01 DK062431NIDDK NIH HHS U01 DK062432NIDDK NIH HHS U24 DK062429NINDS NIH HHS R01 NS049477Wellcome Trust 102974Wellcome Trust WT098051
Abstract
Genome-wide association studies of the related chronic inflammatory bowel diseases (IBD) known as Crohn's disease and ulcerative colitis have shown strong evidence of association to the major histocompatibility complex (MHC). This region encodes a large number of immunological candidates, including the antigen-presenting classical human leukocyte antigen (HLA) molecules. Studies in IBD have indicated that multiple independent associations exist at HLA and non-HLA genes, but they have lacked the statistical power to define the architecture of association and causal alleles. To address this, we performed high-density SNP typing of the MHC in >32,000 individuals with IBD, implicating multiple HLA alleles, with a primary role for HLA-DRB1*01:03 in both Crohn's disease and ulcerative colitis. Noteworthy differences were observed between these diseases, including a predominant role for class II HLA variants and heterozygous advantage observed in ulcerative colitis, suggesting an important role of the adaptive immune response in the colonic environment in the pathogenesis of IBD.
Indexed as
Polymorphism, Single NucleotideAllelesChromosome MappingColitis, UlcerativeCrohn DiseaseGenetic LinkageGenetic Predisposition to DiseaseGenome-Wide Association StudyGenotypeGenotyping TechniquesHeterozygoteHLA-DRB1 ChainsHumansInflammatory Bowel DiseasesMajor Histocompatibility ComplexPhenotypeHLA-DRB1*01 antigenHLA-DRB1 Chains
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