Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disorders.
Kennedy, Nicholas A
Skogholt, Anne Heidi
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Eijsbouts, C., Zheng, T., Kennedy, N. A., Bonfiglio, F., Anderson, C. A., Moutsianas, L., Holliday, J., et al. (2021). Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disorders.. Nature genetics, 53 (11), 1543-1552. https://doi.org/10.1038/s41588-021-00950-8
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<sub>g</sub> > 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.
Vetenskapsrådet (Swedish Research Council) (2017-02403)
Wellcome Trust (098051, 098051)
DH | National Institute for Health Research (NIHR) (BRC-1215-20007, BRC-1215-20008, BRC-1215-20003, BRC-1215-20014)
U.S. Department of Health & Human Services | National Institutes of Health (NIH) (R01 DK 92179 and 115950)
NIDDK NIH HHS (R01 DK092179)
European Research Council (715772)
External DOI: https://doi.org/10.1038/s41588-021-00950-8
This record's URL: https://www.repository.cam.ac.uk/handle/1810/332043
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/