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

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MARC

Eijsbouts, C.University of Oxford (author)

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

Article/chapterEnglish2021

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2021-11-05
Springer Science and Business Media LLC,2021

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LIBRIS-ID:oai:gup.ub.gu.se/315468
https://gup.ub.gu.se/publication/315468URI
https://doi.org/10.1038/s41588-021-00950-8DOI
https://lup.lub.lu.se/record/eaed7d99-033e-4549-9b96-66d4ef218fbeURI
http://kipublications.ki.se/Default.aspx?queryparsed=id:148200898URI

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Language:English

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Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

Notes

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 (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. © 2021, The Author(s).

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Zheng, T. (author)
Kennedy, N. A. (author)
Bonfiglio, F.Karolinska Institutet (author)
Anderson, C. A. (author)
Moutsianas, L. (author)
Holliday, J. (author)
Shi, J. (author)
Shringarpure, S. (author)
Agee, M. (author)
Aslibekyan, S. (author)
Auton, A. (author)
Bell, R. K. (author)
Bryc, K. (author)
Clark, S. K. (author)
Elson, S. L. (author)
Fletez-Brant, K. (author)
Fontanillas, P. (author)
Furlotte, N. A. (author)
Gandhi, P. M.University of Cambridge,Cambridge University Hospitals NHS Foundation Trust (author)
Heilbron, K. (author)
Hicks, B. (author)
Hinds, D. A. (author)
Huber, K. E. (author)
Jewett, E. M. (author)
Jiang, Y. (author)
Kleinman, A. (author)
Lin, K. H. (author)
Litterman, N. K. (author)
Luff, M. K. (author)
McCreight, J. C. (author)
McIntyre, M. H. (author)
McManus, K. F. (author)
Mountain, J. L.University of Oxford (author)
Mozaffari, S. V. (author)
Nandakumar, P. (author)
Noblin, E. S. (author)
Northover, C. A. M. (author)
O’Connell, J. (author)
Petrakovitz, A. A. (author)
Pitts, S. J. (author)
Poznik, G. D. (author)
Sathirapongsasuti, J. F. (author)
Shastri, A. J. (author)
Shelton, J. F. (author)
Tian, C. (author)
Tung, J. Y. (author)
Tunney, R. J. (author)
Vacic, V. (author)
Wang, X. (author)
Zare, A. S. (author)
Voda, A. I. (author)
Kashyap, P. (author)
Chang, L. (author)
Mayer, E. (author)
Heitkemper, M. (author)
Sayuk, G. S. (author)
Ringel-Kulka, T. (author)
Ringel, Y. (author)
Chey, W. D. (author)
Eswaran, S. (author)
Merchant, J. L. (author)
Shulman, R. J. (author)
Bujanda, L. (author)
Garcia-Etxebarria, K. (author)
Dlugosz, A.Karolinska Institutet,Basque Foundation for Science,Biodonostia Health Research Institute,Monash University (author)
Lindberg, G. (author)
Schmidt, P. T. (author)
Karling, P. (author)
Ohlsson, BodilLund University,Lunds universitet,Internmedicin - epidemiologi,Forskargrupper vid Lunds universitet,Internal Medicine - Epidemiology,Lund University Research Groups(Swepub:lu)kir-boh (author)
Walter, S. (author)
Faresjö, Å O. (author)
Simrén, Magnus,1966Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition(Swepub:gu)xsimrm (author)
Halfvarson, J. (author)
Portincasa, P. (author)
Barbara, G. (author)
Usai-Satta, P. (author)
Neri, M. (author)
Nardone, G. (author)
Cuomo, R. (author)
Galeazzi, F. (author)
Bellini, M. (author)
Latiano, A. (author)
Houghton, L. (author)
Jonkers, D. (author)
Kurilshikov, A. (author)
Weersma, R. K. (author)
Netea, M. (author)
Tesarz, J. (author)
Gauss, A. (author)
Goebel-Stengel, M. (author)
Andresen, V. (author)
Frieling, T. (author)
Pehl, C. (author)
Schaefert, R. (author)
Niesler, B. (author)
Lieb, W. (author)
Hanevik, K. (author)
Langeland, N. (author)
Wensaas, K. A. (author)
Litleskare, S. (author)
Gabrielsen, M. E. (author)
Thomas, L. (author)
Thijs, V. (author)
Lemmens, R. (author)
Van Oudenhove, L. (author)
Wouters, M. (author)
Farrugia, G. (author)
Franke, A. (author)
Hübenthal, M. (author)
Abecasis, G. (author)
Zawistowski, M. (author)
Skogholt, A. H. (author)
Ness-Jensen, E.Karolinska Institutet (author)
Hveem, K. (author)
Esko, T. (author)
Teder-Laving, M. (author)
Zhernakova, A. (author)
Camilleri, M. (author)
Boeckxstaens, G. (author)
Whorwell, P. J. (author)
Spiller, R. (author)
McVean, G. (author)
D’Amato, M. (author)
Jostins, L. (author)
Parkes, M. (author)
Karolinska InstitutetUniversity of Oxford (creator_code:org_t)
et al.

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In:Nature Genetics: Springer Science and Business Media LLC53:11, s. 1543-15521061-40361546-1718

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By the author/editor: Eijsbouts, C.; Zheng, T.; Kennedy, N. A.; Bonfiglio, F.; Anderson, C. A.; Moutsianas, L.; show more...; Holliday, J.; Shi, J.; Shringarpure, S.; Agee, M.; Aslibekyan, S.; Auton, A.; Bell, R. K.; Bryc, K.; Clark, S. K.; Elson, S. L.; Fletez-Brant, K.; Fontanillas, P.; Furlotte, N. A.; Gandhi, P. M.; Heilbron, K.; Hicks, B.; Hinds, D. A.; Huber, K. E.; Jewett, E. M.; Jiang, Y.; Kleinman, A.; Lin, K. H.; Litterman, N. K.; Luff, M. K.; McCreight, J. C.; McIntyre, M. H.; McManus, K. F.; Mountain, J. L.; Mozaffari, S. V.; Nandakumar, P.; Noblin, E. S.; Northover, C. A. ...; O’Connell, J.; Petrakovitz, A. ...; Pitts, S. J.; Poznik, G. D.; Sathirapongsasut ...; Shastri, A. J.; Shelton, J. F.; Tian, C.; Tung, J. Y.; Tunney, R. J.; Vacic, V.; Wang, X.; Zare, A. S.; Voda, A. I.; Kashyap, P.; Chang, L.; Mayer, E.; Heitkemper, M.; Sayuk, G. S.; Ringel-Kulka, T.; Ringel, Y.; Chey, W. D.; Eswaran, S.; Merchant, J. L.; Shulman, R. J.; Bujanda, L.; Garcia-Etxebarri ...; Dlugosz, A.; Lindberg, G.; Schmidt, P. T.; Karling, P.; Ohlsson, Bodil; Walter, S.; Faresjö, Å O.; Simrén, Magnus, ...; Halfvarson, J.; Portincasa, P.; Barbara, G.; Usai-Satta, P.; Neri, M.; Nardone, G.; Cuomo, R.; Galeazzi, F.; Bellini, M.; Latiano, A.; Houghton, L.; Jonkers, D.; Kurilshikov, A.; Weersma, R. K.; Netea, M.; Tesarz, J.; Gauss, A.; Goebel-Stengel, ...; Andresen, V.; Frieling, T.; Pehl, C.; Schaefert, R.; Niesler, B.; Lieb, W.; Hanevik, K.; Langeland, N.; Wensaas, K. A.; Litleskare, S.; Gabrielsen, M. E ...; Thomas, L.; Thijs, V.; Lemmens, R.; Van Oudenhove, L ...; Wouters, M.; Farrugia, G.; Franke, A.; Hübenthal, M.; Abecasis, G.; Zawistowski, M.; Skogholt, A. H.; Ness-Jensen, E.; Hveem, K.; Esko, T.; Teder-Laving, M.; Zhernakova, A.; Camilleri, M.; Boeckxstaens, G.; Whorwell, P. J.; Spiller, R.; McVean, G.; D’Amato, M.; Jostins, L.; Parkes, M.; show less...

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