ArticleNature genetics2021
Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disorders.
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Article in Nature genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 153 papers, 7 of them syntheses that pooled it.
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153citing papers in PubMed, 7 pooled it
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Who cites it
153 citing papers in PubMed, 7 syntheses or guidelines pooled it.
- Pooled it
- Association between myalgic encephalomyelitis/chronic fatigue syndrome and irritable bowel syndrome: a systematic review and meta-analysis.Frontiers in medicine · 2026Pooled it
- Gastrointestinal traits, common inflammatory disorders, gallstones, and biliary tract cancer: A network Mendelian randomization study.Journal of advanced research · 2026Pooled it
- Is there a bidirectional relationship between allergic rhinitis and irritable bowel syndrome? A meta-analysis.Journal of global health · 2025Pooled it
- Major depressive disorder and the risk of irritable bowel syndrome: A Mendelian randomization study.Molecular genetics & genomic medicine · 2024Pooled it
- Causality of genetically determined blood metabolites on irritable bowel syndrome: A Mendelian randomization study.PloS one · 2024Pooled it
- Positive psychological well-being and clinical characteristics in IBS: A systematic review.General hospital psychiatryPooled it
- Decoding IBS: a machine learning approach to psychological distress and gut-brain interaction.BMC gastroenterology · 2024Trial
- Irritable bowel syndrome.Nature reviews. Disease primers · 2026Review
- Single-cell profiling and genetic regulation of alternative polyadenylation in the human brain.Nature genetics · 2026Article
- Bidirectional causal associations between Sjögren syndrome and gastrointestinal disorders: A two-sample Mendelian randomization study.Medicine · 2026Article
- Irritable Bowel Syndrome and Incident Hypertension: Epidemiologic and Genetic Insights.Biomedicines · 2026Article
- Neuronal Cell-Specific sc-eQTL and Integrative eQTL-pQTL Mendelian Randomization Prioritize CKAP2 as a Candidate Gene for Major Depressive Disorder.Journal of molecular neuroscience : MN · 2026Observational
- Intestinal muscularis in health and disease.Communications biology · 2026Review
- A lesion-derived brain network of somatic symptoms for transdiagnostic individual application.BMC medicine · 2026Article
- Pleiotropic shared heritability quantifies the shared genetic variance of common diseases.Nature genetics · 2026Article
- Causal relationships between irritable bowel syndrome and brain functional networks: A Mendelian randomization study.Journal of translational internal medicine · 2026Article
- Bidirectional causal association between cathepsins and neuropsychiatric disorders: univariate and multivariate Mendelian randomization study.European archives of psychiatry and clinical neuroscience · 2026Article
- Association between social isolation, loneliness and the incidence of irritable bowel syndrome: a prospective cohort study in the UK Biobank.Annals of general psychiatry · 2026Article
- Screening for irritable bowel syndrome and its associated factors among patients with type 2 diabetes mellitus attending outpatient clinics in Jeddah, Saudi Arabia: A cross-sectional study.Journal of family medicine and primary care · 2026Article
93 more citing papers are in PubMed but not listed here.
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Authors and funding
31 authors.
Chris EijsboutsBig Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0001-5179-0653
Tenghao Zheng *Center for Molecular Medicine & Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
Nicholas A Kennedy *IBD Pharmacogenetics, College of Medicine and Health, University of Exeter, Exeter, UK.
Ferdinando BonfiglioCenter for Molecular Medicine & Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
Carl A AndersonWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.ORCID http://orcid.org/0000-0003-1719-7009
Loukas MoutsianasWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.ORCID http://orcid.org/0000-0001-5453-345X
Joanne HollidayNuffield Department of Population Health, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0003-4568-7320
Jingchunzi Shi23andMe, Inc., Sunnyvale, CA, USA.
Suyash Shringarpure23andMe, Inc., Sunnyvale, CA, USA.ORCID http://orcid.org/0000-0001-6464-2668
23andMe Research Team
Alexandru-Ioan VodaKennedy Institute of Rheumatology, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0003-2974-6992
Bellygenes Initiative
Gianrico FarrugiaEnteric NeuroScience Program, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN, USA.ORCID http://orcid.org/0000-0003-3473-5235
Andre FrankeInstitute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
Matthias HübenthalInstitute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.ORCID http://orcid.org/0000-0002-5956-3006
Gonçalo AbecasisDepartment of Biostatistics, University of Michigan, School of Public Health, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0003-1509-1825
Matthew ZawistowskiDepartment of Biostatistics, University of Michigan, School of Public Health, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0002-3005-083X
Anne Heidi SkogholtDepartment of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway.
Eivind Ness-JensenDepartment of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway.ORCID http://orcid.org/0000-0001-6005-0729
Kristian HveemDepartment of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway.
Tõnu EskoEstonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia.
Maris Teder-LavingEstonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia.ORCID http://orcid.org/0000-0002-5872-1850
Alexandra ZhernakovaDepartment of Genetics, University Medical Center Groningen, Groningen, the Netherlands.
Michael CamilleriClinical Enteric Neuroscience Translational and Epidemiological Research and Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN, USA.ORCID http://orcid.org/0000-0001-6472-7514
Guy BoeckxstaensDavid Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Peter J WhorwellNeurogastroenterology Unit, Wythenshawe Hospital, Centre for Gastrointestinal Sciences, University of Manchester, Manchester, UK.ORCID http://orcid.org/0000-0002-5220-8474
Robin SpillerNottingham Digestive Diseases Centre, National Institute for Health Research Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK.ORCID http://orcid.org/0000-0001-6371-4500
Gil McVeanBig Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-5012-4162
Mauro D'AmatoCenter for Molecular Medicine & Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden. mdamato@cicbiogune.es.ORCID http://orcid.org/0000-0003-2743-5197
Luke JostinsBig Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK. luke.jostins@kennedy.ox.ac.uk.ORCID http://orcid.org/0000-0002-2475-3969
Miles ParkesDivision of Gastroenterology and Hepatology, Department of Medicine, University of Cambridge, Cambridge, UK. miles.parkes@addenbrookes.nhs.uk.ORCID http://orcid.org/0000-0002-6467-0631
Funding
Mechanisms of alteration of GI physiology by gut microbesR01DK114007 · NIDDK · MAYO CLINIC ROCHESTER · PI Purna C Kashyap · 2017 to 2026
$4.7MBile Acids, Genetic Control and Colonic Function in Irritable Bowel SyndromeR01DK092179 · NIDDK · MAYO CLINIC ROCHESTER · PI CAMILLERI, MICHAEL L. · 2011 to 2015
$1.8MCancer Research UK 16896Medical Research Council MC_G1002464Medical Research Council MC_PC_17228Medical Research Council MC_QA137853NIDDK NIH HHS R01 DK092179NIDDK NIH HHS R01 DK114007Wellcome Trust 093885/Z/10/ZWellcome Trust 098051Wellcome Trust 208750/Z/17/ZWellcome Trust 215097/Z/18/Z
Abstract
Irritable bowel syndrome (IBS) results from disordered brain-gut interactions. Identifying susceptibility genes could highlight the underlying pathophysiological mechanisms. We designed a digestive health questionnaire for UK Biobank and combined identified cases with IBS with independent cohorts. We conducted a genome-wide association study with 53,400 cases and 433,201 controls and replicated significant associations in a 23andMe panel (205,252 cases and 1,384,055 controls). Our study identified and confirmed six genetic susceptibility loci for IBS. Implicated genes included NCAM1, CADM2, PHF2/FAM120A, DOCK9, CKAP2/TPTE2P3 and BAG6. The first four are associated with mood and anxiety disorders, expressed in the nervous system, or both. Mirroring this, we also found strong genome-wide correlation between the risk of IBS and anxiety, neuroticism and depression (r
Indexed as
AgedAnxiety DisordersCD56 AntigenCell Adhesion MoleculesCytoskeletal ProteinsFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyGuanine Nucleotide Exchange FactorsHomeodomain ProteinsHumansIrritable Bowel SyndromeMaleMiddle AgedMolecular ChaperonesMood DisordersBAG6 protein, humanCADM2 protein, humanCD56 AntigenCell Adhesion MoleculesCKAP2 protein, humanCytoskeletal ProteinsDOCK9 protein, humanGuanine Nucleotide Exchange FactorsHomeodomain ProteinsMolecular ChaperonesNCAM1 protein, humanPHF2 protein, human
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