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Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disorders.

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cam.issuedOnline2021-11-05
dc.contributor.authorEijsbouts, Chris
dc.contributor.authorZheng, Tenghao
dc.contributor.authorKennedy, Nicholas A
dc.contributor.authorBonfiglio, Ferdinando
dc.contributor.authorAnderson, Carl A
dc.contributor.authorMoutsianas, Loukas
dc.contributor.authorHolliday, Joanne
dc.contributor.authorShi, Jingchunzi
dc.contributor.authorShringarpure, Suyash
dc.contributor.author23andMe Research Team
dc.contributor.authorVoda, Alexandru-Ioan
dc.contributor.authorBellygenes Initiative
dc.contributor.authorFarrugia, Gianrico
dc.contributor.authorFranke, Andre
dc.contributor.authorHübenthal, Matthias
dc.contributor.authorAbecasis, Gonçalo
dc.contributor.authorZawistowski, Matthew
dc.contributor.authorSkogholt, Anne Heidi
dc.contributor.authorNess-Jensen, Eivind
dc.contributor.authorHveem, Kristian
dc.contributor.authorEsko, Tõnu
dc.contributor.authorTeder-Laving, Maris
dc.contributor.authorZhernakova, Alexandra
dc.contributor.authorCamilleri, Michael
dc.contributor.authorBoeckxstaens, Guy
dc.contributor.authorWhorwell, Peter J
dc.contributor.authorSpiller, Robin
dc.contributor.authorMcVean, Gil
dc.contributor.authorD'Amato, Mauro
dc.contributor.authorJostins, Luke
dc.contributor.authorParkes, Miles
dc.contributor.orcidEijsbouts, Chris [0000-0001-5179-0653]
dc.contributor.orcidAnderson, Carl A [0000-0003-1719-7009]
dc.contributor.orcidMoutsianas, Loukas [0000-0001-5453-345X]
dc.contributor.orcidHolliday, Joanne [0000-0003-4568-7320]
dc.contributor.orcidShringarpure, Suyash [0000-0001-6464-2668]
dc.contributor.orcidVoda, Alexandru-Ioan [0000-0003-2974-6992]
dc.contributor.orcidFarrugia, Gianrico [0000-0003-3473-5235]
dc.contributor.orcidHübenthal, Matthias [0000-0002-5956-3006]
dc.contributor.orcidAbecasis, Gonçalo [0000-0003-1509-1825]
dc.contributor.orcidZawistowski, Matthew [0000-0002-3005-083X]
dc.contributor.orcidNess-Jensen, Eivind [0000-0001-6005-0729]
dc.contributor.orcidTeder-Laving, Maris [0000-0002-5872-1850]
dc.contributor.orcidCamilleri, Michael [0000-0001-6472-7514]
dc.contributor.orcidWhorwell, Peter J [0000-0002-5220-8474]
dc.contributor.orcidSpiller, Robin [0000-0001-6371-4500]
dc.contributor.orcidMcVean, Gil [0000-0002-5012-4162]
dc.contributor.orcidD'Amato, Mauro [0000-0003-2743-5197]
dc.contributor.orcidJostins, Luke [0000-0002-2475-3969]
dc.contributor.orcidParkes, Miles [0000-0002-6467-0631]
dc.date.accessioned2022-01-05T16:28:58Z
dc.date.available2022-01-05T16:28:58Z
dc.date.issued2021-11
dc.date.updated2022-01-05T16:28:57Z
dc.description.abstractIrritable 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 (rg > 0.5). Additional analyses suggested this arises due to shared pathogenic pathways rather than, for example, anxiety causing abdominal symptoms. Implicated mechanisms require further exploration to help understand the altered brain-gut interactions underlying IBS.
dc.identifier.doi10.17863/CAM.79490
dc.identifier.eissn1546-1718
dc.identifier.issn1061-4036
dc.identifier.otherPMC8571093
dc.identifier.other34741163
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/332043
dc.languageeng
dc.language.isoeng
dc.publisherSpringer Science and Business Media LLC
dc.publisher.urlhttp://dx.doi.org/10.1038/s41588-021-00950-8
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourceessn: 1546-1718
dc.sourcenlmid: 9216904
dc.subjectAged
dc.subjectAnxiety Disorders
dc.subjectCD56 Antigen
dc.subjectCell Adhesion Molecules
dc.subjectCytoskeletal Proteins
dc.subjectFemale
dc.subjectGenetic Predisposition to Disease
dc.subjectGenome-Wide Association Study
dc.subjectGuanine Nucleotide Exchange Factors
dc.subjectHomeodomain Proteins
dc.subjectHumans
dc.subjectIrritable Bowel Syndrome
dc.subjectMale
dc.subjectMiddle Aged
dc.subjectMolecular Chaperones
dc.subjectMood Disorders
dc.subjectPolymorphism, Single Nucleotide
dc.subjectUnited Kingdom
dc.titleGenome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disorders.
dc.typeArticle
dcterms.dateAccepted2021-09-08
prism.endingPage1552
prism.issueIdentifier11
prism.publicationNameNat Genet
prism.startingPage1543
prism.volume53
pubs.funder-project-idNational Institute for Health and Care Research (IS-BRC-1215-20014)
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1038/s41588-021-00950-8

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