Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disorders
Creators: name: Eijsbouts, Chris
name: Zheng, Tenghao
name: Kennedy, Nicholas A.
name: Bonfiglio, Ferdinando
name: Anderson, Carl A.
name: Moutsianas, Loukas
name: Holliday, Joanne
name: Shi, Jingchunzi
name: Shringarpure, Suyash
name: Voda, Alexandru-Ioan
name: Farrugia, Gianrico
name: Franke, Andre
name: Hübenthal, Matthias
name: Abecasis, Gonçalo
name: Zawistowski, Matthew
name: Skogholt, Anne Heidi
name: Ness-Jensen, Eivind
name: Hveem, Kristian
name: Esko, Tõnu
name: Teder-Laving, Maris
name: Zhernakova, Alexandra
name: Camilleri, Michael
name: Boeckxstaens, Guy
name: Whorwell, Peter J.
name: Spiller, Robin
name: McVean, Gil
name: D’Amato, Mauro
name: Jostins, Luke
name: Parkes, Miles
name: Agee, Michelle
name: Aslibekyan, Stella
name: Auton, Adam
name: Bell, Robert K.
name: Bryc, Katarzyna
name: Clark, Sarah K.
name: Elson, Sarah L.
name: Fletez-Brant, Kipper
name: Fontanillas, Pierre
name: Furlotte, Nicholas A.
name: Gandhi, Pooja M.
name: Heilbron, Karl
name: Hicks, Barry
name: Hinds, David A.
name: Huber, Karen E.
name: Jewett, Ethan M.
name: Jiang, Yunxuan
name: Kleinman, Aaron
name: Lin, Keng-Han
name: Litterman, Nadia K.
name: Luff, Marie K.
name: McCreight, Jey C.
name: McIntyre, Matthew H.
name: McManus, Kimberly F.
name: Mountain, Joanna L.
name: Mozaffari, Sahar V.
name: Nandakumar, Priyanka
name: Noblin, Elizabeth S.
name: Northover, Carrie A. M.
name: O’Connell, Jared
name: Petrakovitz, Aaron A.
name: Pitts, Steven J.
name: Poznik, G. David
name: Sathirapongsasuti, J. Fah
name: Shastri, Anjali J.
name: Shelton, Janie F.
name: Tian, Chao
name: Tung, Joyce Y.
name: Tunney, Robert J.
name: Vacic, Vladimir
name: Wang, Xin
name: Zare, Amir S.
name: Kashyap, Purna
name: Chang, Lin
name: Mayer, Emeran
name: Heitkemper, Margaret
name: Sayuk, Gregory S.
name: Ringel-Kulka, Tamar
name: Ringel, Yehuda
name: Chey, William D.
name: Eswaran, Shanti
name: Merchant, Juanita L.
name: Shulman, Robert J.
name: Bujanda, Luis
name: Garcia-Etxebarria, Koldo
name: Dlugosz, Aldona
name: Lindberg, Greger
name: Schmidt, Peter T.
name: Karling, Pontus
name: Ohlsson, Bodil
name: Walter, Susanna
name: Faresjö, Åshild O.
name: Simren, Magnus
name: Halfvarson, Jonas
name: Portincasa, Piero
name: Barbara, Giovanni
name: Usai-Satta, Paolo
name: Neri, Matteo
name: Nardone, Gerardo
name: Cuomo, Rosario
name: Galeazzi, Francesca
name: Bellini, Massimo
name: Latiano, Anna
name: Houghton, Lesley
name: Jonkers, Daisy
name: Kurilshikov, Alexander
name: Weersma, Rinse K.
name: Netea, Mihai
name: Tesarz, Jonas
name: Gauss, Annika
name: Goebel-Stengel, Miriam
name: Andresen, Viola
name: Frieling, Thomas
name: Pehl, Christian
name: Schaefert, Rainer
name: Niesler, Beate
name: Lieb, Wolfgang
name: Hanevik, Kurt
name: Langeland, Nina
name: Wensaas, Knut-Arne
name: Litleskare, Sverre
name: Gabrielsen, Maiken E.
name: Thomas, Laurent
name: Thijs, Vincent
name: Lemmens, Robin
name: Van Oudenhove, Lukas
name: Wouters, Mira
Publisher: name: Apollo - University of Cambridge Repository
Year: 2021
Subjects: Article
/631/208/205/2138
/692/699/1503/1502/2071
/692/699/476
/38/43
article

description: Funder: Kennedy Trust Rheumatology Research Prize Studentship
description: Funder: DFG Cluster of Excellence “Precision Medicine in Chronic In-flammation” (PMI; ID: EXC2167)
description: Funder: EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: “Ideas” Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013)); doi: https://doi.org/10.13039/100011199; Grant(s): 715772
description: Funder: NWO-VIDI grant 016.178.056, the Netherlands Heart Foundation CVON grant 2018-27, and NWO Gravitation grant ExposomeNL
description: Funder: Li Ka Shing Foundation (Li Ka Shing Foundation Limited); doi: https://doi.org/10.13039/100007421
description: 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 (rg &gt; 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.