ArticleNature genetics2022
Large-scale sequencing identifies multiple genes and rare variants associated with Crohn's disease susceptibility.
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Article in Nature genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 127 papers, 6 of them syntheses that pooled it.
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127citing papers in PubMed, 6 pooled it
32.4field-weighted citation impact, top 1% of its field
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Who cites it
127 citing papers in PubMed, 6 syntheses or guidelines pooled it, 176 citations in OpenAlex.
- Association Between Keratoconus and Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.Cornea · 2026Pooled it
- Meta-analysis across six global biobanks identifies recessive coding associations with complex traits and diseases.American journal of human genetics · 2026Pooled it
- Oxidative stress gene expression, DNA methylation, and gut microbiota interaction trigger Crohn's disease: a multi-omics Mendelian randomization study.BMC medicine · 2023Pooled it
- Trans-ancestry, Bayesian meta-analysis discovers 20 novel risk loci for inflammatory bowel disease in an African American, East Asian and European cohort.Human molecular genetics · 2023Pooled it
- Genome-wide analyses of ADHD identify 27 risk loci, refine the genetic architecture and implicate several cognitive domains.Nature genetics · 2023Pooled it
- Chromosomal Numerical Aberrations and Rare Copy Number Variation in Patients with Inflammatory Bowel Disease.Journal of Crohn's & colitis · 2023Pooled it
- Trial
- Defined human Clostridia consortia reverse colitis via dual effects of tryptophan metabolites on microbiota and immunity.Cell host & microbe · 2026Article
- A functional immune-based platform for donor-recipient matching in faecal microbiota transplantation for inflammatory bowel disease.EBioMedicine · 2026Article
- Cell-type specific analyses in blood and gut identify cis-eQTL matching 140 IBD risk loci and entrectinib as repurposing candidate.Nature communications · 2026Article
- Gut mucosal barrier: the frontline of bidirectional regulation of the gut-X axis.Medical review (2021) · 2026Review
- High-resolution promoter interaction analysis implicates genes involved in activation of type 3 innate lymphoid cells in immune disease risk.Nature genetics · 2026Article
- Article
- Mapping mesenchymal diversity in the human small intestine and organoids.Nature cell biology · 2026Article
- Machine Learning Reveals the Contribution of Rare Genetic Variants and Enhances Risk Prediction for Coronary Artery Disease in the Japanese Population.Circulation. Genomic and precision medicine · 2026Article
- Microbiome-metabolite signaling networks in gastrointestinal disease: systems biology, network rewiring, and precision therapeutics.Archives of microbiology · 2026Review
- Crohn's Disease: From Immune Dysregulation to Intestinal Damage.Inflammation · 2026Review
- WxS-QC-a quality control pipeline for human germline short-variant Whole-Genome and Whole-Exome cohorts for population-scale analyses.Bioinformatics (Oxford, England) · 2026Article
- Single-cell RNA sequencing of terminal ileal biopsies identifies signatures of Crohn's disease pathogenesis.Nature genetics · 2026Article
- Translating IBD Genomics into Clinical Practice.Digestive diseases and sciences · 2026Review
67 more citing papers are in PubMed but not listed here.
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Authors and funding
139 authors at 20 institutions in 12 countries.
Aleksejs Sazonovs *Genomics of Inflammation and Immunity Group, Human Genetics Programme, Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.
Christine R Stevens *Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-2621-2234
Guhan R Venkataraman *Department of Biomedical Data Science, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0003-0754-6631
Kai Yuan *Stanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-8460-6581
Brandon AvilaProgram in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Maria T AbreuCrohn's and Colitis Center, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, USA.
Tariq AhmadRoyal Devon and Exeter Hospital, Exeter, UK.
Matthieu AllezHopital Saint-Louis, APHP, Universite de Paris, INSERM U1160, Paris, France.
Ashwin N AnanthakrishnanDivision of Gastroenterology, Crohn's and Colitis Center, Massachusetts General Hospital, Boston, MA, USA.
Gil AtzmonDepartment for Human Biology, University of Haifa, Haifa, Israel.
Aris BarasRegeneron Genetics Center, Tarrytown, NY, USA.
Jeffrey C BarrettHuman Genetics Programme, Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.
Nir BarzilaiDepartments of Medicine and Genetics, Albert Einstein College of Medicine, Bronx, NY, USA.
Laurent BeaugerieGastroenterology Department, Sorbonne Universite, Saint Antoine Hospital, Paris, France.
Ashley BeechamJohn P. Hussman Institute for Human Genomics, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, USA.
Charles N BernsteinUniversity of Manitoba, Winnipeg, Manitoba, Canada.
Alain BittonMcGill University and McGill University Health Centre, Montreal, Quebec, Canada.
Bernd BokemeyerDepartment of Internal Medicine, University Medical Center Schleswig-Holstein, Kiel, Germany.
Andrew ChanClinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, MA, USA.
Daniel ChungMassachusetts General Hospital, Boston, MA, USA.
Isabelle CleynenDepartment of Human Genetics, KU Leuven, Leuven, Belgium.
Jacques CosnesProfesseur Chef de Service chez APHP and Universite Paris-6, Paris, France.
David J CutlerDepartment of Human Genetics, Emory University, Atlanta, GA, USA.
Allan DalyHuman Genetics Informatics, Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.
Oriana M DamasUniversity of Miami, Miami, FL, USA.
Lisa W DattaMeyerhoff Inflammatory Bowel Disease Center, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Noor DawanyChildren's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA, USA.
Marcella DevotoChildren's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA, USA.
Sheila DodgeGenomics Platform, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Eva EllinghausChristian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany.
Laura FachalGenomics of Inflammation and Immunity Group, Human Genetics Programme, Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.
Martti FarkkilaHelsinki University Central Hospital, Helsinki, Finland.
William FaubionMayo Clinic, Rochester, Rochester, MN, USA.
Manuel FerreiraRegeneron Genetics Center, Tarrytown, NY, USA.
Denis FranchimontErasme Hospital, ULB, Brussels, Belgium.
Stacey B GabrielGenomics Platform, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Tian GeStanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Michel GeorgesUniversity of Liège, ULG, Liège, Belgium.
Kyle GettlerIcahn School of Medicine at Mount Sinai, New York, NY, USA.
Mamta GiriIcahn School of Medicine at Mount Sinai, New York, NY, USA.
Benjamin GlaserDepartment of Endocrinology and Metabolism, Hadassah Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
Siegfried GoergUniversity Medical Center Schleswig-Holstein, Kiel, Germany.
Philippe GoyetteResearch Center Montreal Heart Institute, Montreal, Quebec, Canada.
Daniel GrahamInfectious Disease and Microbiome Program, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Eija HämäläinenInstitute for Molecular Medicine Finland, FIMM, HiLIFE, University of Helsinki, Helsinki, Finland.
Talin HarituniansF. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars Sinai Medical Center, Los Angeles, CA, USA.
Graham A HeapRoyal Devon and Exeter Hospital, Exeter, UK.
Mikko HiltunenInstitute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
Marc HoeppnerChristian-Albrechts-University of Kiel, Kiel, Germany.
Julie E HorowitzRegeneron Genetics Center, Tarrytown, NY, USA.
Peter IrvingDepartment of Gastroenterology, Guys and Saint Thomas Hospital, London, UK.
Vivek IyerHuman Genetics Informatics, Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.
Chaim JalasDirector of Genetic Resources and Services, Center for Rare Jewish Genetic Disorders, Bonei Olam, Brooklyn, NY, USA.
Judith KelsenChildren's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA, USA.
Hamed KhaliliClinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, MA, USA.
Barbara S KirschnerDepartment of Gastroenterology, University of Chicago Medicine, Chicago, IL, USA.
Kimmo KontulaDepartment of Medicine, Helsinki University Hospital, and Research Program for Clinical and Molecular Metabolism, University of Helsinki, Helsinki, Finland.
Jukka T KoskelaInstitute for Molecular Medicine Finland, FIMM, HiLIFE, University of Helsinki, Helsinki, Finland.
Subra KugathasanEmory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.
Juozas KupcinskasDepartment of Gastroenterology and Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Christopher A LambTranslational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.ORCID http://orcid.org/0000-0002-7271-4956
Matthias LaudesUniversity Medical Center Schleswig-Holstein, Kiel, Germany.
Chloé LévesqueResearch Center Montreal Heart Institute, Montreal, Quebec, Canada.
Adam P LevineUniversity College London, London, UK.
James D LewisPerelman School of Medicine, University of Pennsylvania, Philadelphia, USA.
Claire LiefferinckxErasme Hospital, ULB, Brussels, Belgium.
Britt-Sabina LoescherChristian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany.
Edouard LouisUniversity of Liège, ULG, Liège, Belgium.
John MansfieldTranslational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.
Sandra MayChristian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany.
Jacob L McCauleyJohn P. Hussman Institute for Human Genomics, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, USA.
Emebet MengeshaF. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars Sinai Medical Center, Los Angeles, CA, USA.
Myriam MniUniversity of Liège, ULG, Liège, Belgium.
Paul MoayyediMcMaster University, Hamilton, Ontario, Canada.
Christopher J MoranMassachusetts General Hospital, Boston, MA, USA.
Rodney D NewberryWashington University School of Medicine, St. Louis, MO, USA.
Sirimon O'CharoenCrohn's and Colitis Foundation, New York, NY, USA.
David T OkouEmory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.
Bas OldenburgDepartment of Gastroenterology and Hepatology, University Medical Centre Utrecht, Utrecht, The Netherlands.
Harry OstrerAlbert Einstein College of Medicine, Bronx, NY, USA.
Aarno PalotieProgram in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Jean PaquetteResearch Center Montreal Heart Institute, Montreal, Quebec, Canada.
Joel PekowDepartment of Gastroenterology, University of Chicago Medicine, Chicago, IL, USA.
Inga PeterIcahn School of Medicine at Mount Sinai, New York, NY, USA.
Marieke J PierikDepartment of Gastroenterology and Hepatology, Maastricht University Medical Centre, Maastricht, The Netherlands.
Cyriel Y PonsioenDepartment of Gastroenterology and Hepatology, Amsterdam University Medical Centres, Amsterdam, The Netherlands.
Nikolas PontikosUniversity College London, London, UK.
Natalie PrescottDepartment of Medical and Molecular Genetics, Kings College London, London, UK.
Ann E PulverSchool of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Souad RahmouniUniversity of Liège, ULG, Liège, Belgium.
Daniel L RiceGenomics of Inflammation and Immunity Group, Human Genetics Programme, Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.
Päivi SaavalainenResearch Programs Unit, Immunobiology, University of Helsinki, Helsinki, Finland.
Bruce SandsIcahn School of Medicine at Mount Sinai, New York, NY, USA.
R Balfour SartorCenter for Gastrointestinal Biology and Disease, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
Elena R SchiffUniversity College London, London, UK.
Stefan SchreiberChristian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany.
L Philip SchummDepartment of Public Health Sciences, University of Chicago, Chicago, IL, USA.
Anthony W SegalUniversity College London, London, UK.
Philippe SeksikGastroenterology Department, Sorbonne Universite, Saint Antoine Hospital, Paris, France.
Rasha ShawkyIBD BioResource, NIHR BioResource, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
Shehzad Z SheikhCenter for Gastrointestinal Biology and Disease, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
Mark S SilverbergMount Sinai Hospital, Toronto, Ontario, Canada.
Alison SimmonsMRC Human Immunology Unit, NIHR Biomedical Research Centre, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
Jurgita SkeicevicieneDepartment of Gastroenterology and Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Harry SokolGastroenterology Department, Sorbonne Universite, Saint Antoine Hospital, Paris, France.
Matthew SolomonsonProgram in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Hari SomineniDepartment of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.
Dylan SunRegeneron Genetics Center, Tarrytown, NY, USA.
Stephan TarganF. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars Sinai Medical Center, Los Angeles, CA, USA.
Dan TurnerShaare Zedek Medical Center, Jerusalem, Israel.
Holm H UhligTranslational Gastroenterology Unit and Biomedical Research Centre, Nuffield Department of Clinical Medicine, Experimental Medicine Division, University of Oxford, Oxford, UK.
Andrea E van der MeulenDepartment of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands.
Séverine VermeireUniversity Hospitals Leuven, Leuven, Belgium.
Sare VerstocktDepartment of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium.
Michiel D VoskuilDepartment of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
Harland S WinterMassachusetts General Hospital, Boston, MA, USA.
Justine YoungCrohn's and Colitis Foundation, New York, NY, USA.
Belgium IBD Consortium
Cedars-Sinai IBD
International IBD Genetics Consortium
NIDDK IBD Genetics Consortium
NIHR IBD BioResource
Regeneron Genetics Center
SHARE Consortium
SPARC IBD Network
UK IBD Genetics Consortium
Richard H DuerrUniversity of Pittsburgh, Pittsburgh, PA, USA.
Andre FrankeChristian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany.
Steven R BrantMeyerhoff Inflammatory Bowel Disease Center, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Judy ChoIcahn School of Medicine at Mount Sinai, New York, NY, USA.
Rinse K WeersmaDepartment of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
Miles ParkesDepartment of Gastroenterology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
Ramnik J XavierInfectious Disease and Microbiome Program, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Manuel A RivasDepartment of Biomedical Data Science, Stanford University, Stanford, CA, USA.
John D RiouxResearch Center Montreal Heart Institute, Montreal, Quebec, Canada.
Dermot P B McGovernF. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars Sinai Medical Center, Los Angeles, CA, USA.
Hailiang HuangStanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, MA, USA. hhuang@broadinstitute.org.
Carl A AndersonGenomics of Inflammation and Immunity Group, Human Genetics Programme, Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK. carl.anderson@sanger.ac.uk.
Mark J DalyProgram in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA. mjdaly@broadinstitute.org.
Broad Institute · USWellcome Sanger Institute · GBChristian-Albrechts-Universität zu Kiel · DEMassachusetts General Hospital · USEmory University · USIcahn School of Medicine at Mount Sinai · USMontreal Heart Institute · CARegeneron (United States) · USUniversity College London · GBUniversity of Helsinki · FIUniversity of Liège · BEUniversity of Miami · USAlbert Einstein College of Medicine · USCedars-Sinai Medical Center · USChildren's Hospital of Philadelphia · USCrohn's and Colitis Foundation · USKU Leuven · BESorbonne Université · FRUniversity Hospital Schleswig-Holstein · DEUniversity Medical Center Groningen · NL
Funding
Large Scale Sequencing and Analysis of GenomesU54HG003067 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GABRIEL, STACEY, LANDER, ERIC S · 2004 to 2015
$568.6MCenter for Common Disease GeneticsUM1HG008895 · NHGRI · BROAD INSTITUTE, INC. · PI DALY, MARK JOSEPH, GABRIEL, STACEY · 2016 to 2020
$111.2MPilot & Feasibility ProgramP30DK043351 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI Ramnik J Xavier · 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 MCGOVERN, DERMOT PATRICK · 1992 to 2020
$31.1MWashington University DDRCC Supplemental Equipment RequestP30DK052574 · NIDDK · WASHINGTON UNIVERSITY · PI Jeffrey Wade Brown · 2000 to 2026
$30.8MRole of IL-10 in APC Regulation of Protective vs. Pathogenic T Cell Responses toP01DK094779 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SHEIKH, SHEHZAD Z. · 2013 to 2023
$17.9MUtilizing the Phenomics of IBD to Enhance Gene DiscoveryU01DK062413 · NIDDK · CEDARS-SINAI MEDICAL CENTER · PI Dermot Patrick McGovern · 2002 to 2026
$12.2MEinstein's Nathan Shock Center of Excellence in Basic Biology of AgingP30AG038072 · NIA · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI VIJG, JAN · 2010 to 2024
$10.8MIBD Gene Mapping by Clinical and Population SubsetsU01DK062431 · NIDDK · RUTGERS BIOMEDICAL AND HEALTH SCIENCES · PI Steven R Brant · 2002 to 2026
$10.7MGene discoveries in subjects with Crohn's disease of African descentR01DK087694 · NIDDK · EMORY UNIVERSITY · PI KUGATHASAN, SUBRA · 2011 to 2023
$10.3MUniversite de Montreal IBD Genetics Research CenterU01DK062432 · NIDDK · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI John D. Rioux · 2002 to 2026
$9.6MNIDDK IBD Genetics Consortium Genetic Research CenterU01DK062420 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI DUERR, RICHARD H · 2002 to 2021
$7.8MDepartment of HealthMedical Research Council MC_PC_MR/S025952/1Medical Research Council MC_UU_00008/7Medical Research Council MC_UU_12010/7Medical Research Council MR/M00533X/1Medical Research Council MR/S036377/1NHGRI NIH HHS R01 HG010140NHGRI NIH HHS U01 HG009080NHGRI NIH HHS U54 HG003067NHGRI NIH HHS UM1 HG008895NIA NIH HHS P30 AG038072NIDDK NIH HHS K01 DK114379NIDDK NIH HHS K23 DK117054NIDDK NIH HHS P01 DK046763NIDDK NIH HHS P01 DK094779NIDDK NIH HHS P30 DK043351NIDDK NIH HHS P30 DK052574NIDDK NIH HHS R01 DK087694NIDDK NIH HHS R01 DK104844NIDDK NIH HHS R01 DK111843NIDDK NIH HHS R01 DK127044NIDDK NIH HHS U01 DK062413NIDDK NIH HHS U01 DK062420NIDDK NIH HHS U01 DK062423NIDDK NIH HHS U01 DK062431NIDDK NIH HHS U01 DK062432Wellcome Trust 108413/A/15/DWellcome Trust 206194
Abstract
Genome-wide association studies (GWASs) have identified hundreds of loci associated with Crohn's disease (CD). However, as with all complex diseases, robust identification of the genes dysregulated by noncoding variants typically driving GWAS discoveries has been challenging. Here, to complement GWASs and better define actionable biological targets, we analyzed sequence data from more than 30,000 patients with CD and 80,000 population controls. We directly implicate ten genes in general onset CD for the first time to our knowledge via association to coding variation, four of which lie within established CD GWAS loci. In nine instances, a single coding variant is significantly associated, and in the tenth, ATG4C, we see additionally a significantly increased burden of very rare coding variants in CD cases. In addition to reiterating the central role of innate and adaptive immune cells as well as autophagy in CD pathogenesis, these newly associated genes highlight the emerging role of mesenchymal cells in the development and maintenance of intestinal inflammation.
Indexed as
Crohn DiseaseGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansPolymorphism, Single Nucleotide
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