TY - JOUR
T1 - Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disorders
AU - The Bellygenes Initiative
AU - 23andMe Research Team
AU - Eijsbouts, Chris
AU - Zheng, Tenghao
AU - Kennedy, Nicholas A.
AU - Bonfiglio, Ferdinando
AU - Anderson, Carl A.
AU - Moutsianas, Loukas
AU - Holliday, Joanne
AU - Shi, Jingchunzi
AU - Shringarpure, Suyash
AU - Agee, Michelle
AU - Aslibekyan, Stella
AU - Auton, Adam
AU - Bell, Robert K.
AU - Bryc, Katarzyna
AU - Clark, Sarah K.
AU - Elson, Sarah L.
AU - Fletez-Brant, Kipper
AU - Fontanillas, Pierre
AU - Furlotte, Nicholas A.
AU - Gandhi, Pooja M.
AU - Heilbron, Karl
AU - Hicks, Barry
AU - Hinds, David A.
AU - Huber, Karen E.
AU - Jewett, Ethan M.
AU - Jiang, Yunxuan
AU - Kleinman, Aaron
AU - Lin, Keng Han
AU - Litterman, Nadia K.
AU - Luff, Marie K.
AU - McCreight, Jey C.
AU - McIntyre, Matthew H.
AU - McManus, Kimberly F.
AU - Mountain, Joanna L.
AU - Mozaffari, Sahar V.
AU - Nandakumar, Priyanka
AU - Noblin, Elizabeth S.
AU - Northover, Carrie A.M.
AU - O’Connell, Jared
AU - Petrakovitz, Aaron A.
AU - Pitts, Steven J.
AU - Poznik, G. David
AU - Sathirapongsasuti, J. Fah
AU - Shastri, Anjali J.
AU - Shelton, Janie F.
AU - Tian, Chao
AU - Tung, Joyce Y.
AU - Tunney, Robert J.
AU - Vacic, Vladimir
AU - Merchant, Juanita L.
N1 - Publisher Copyright: © 2021, The Author(s).
PY - 2021/11
Y1 - 2021/11
N2 - 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.
AB - 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.
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U2 - 10.1038/s41588-021-00950-8
DO - 10.1038/s41588-021-00950-8
M3 - Article
C2 - 34741163
SN - 1061-4036
VL - 53
SP - 1543
EP - 1552
JO - Nature Genetics
JF - Nature Genetics
IS - 11
ER -