Publication type
Journal Article
Authors
- Chris Eijsbouts
- Tenghao Zheng
- Nicholas A. Kennedy
- Ferdinando Bonfiglio
- Carl A. Anderson
- Loukas Moutsianas
- Joanne Holliday
- Jingchunzi Shi
- Suyash Shringarpure
- Alexandru-Ioan Voda
- Gianrico Farrugia
- Andre Franke
- Matthias Hübenthal
- Gonçalo Abecasis
- Matthew Zawistowski
- Anne Heidi Skogholt
- Eivind Ness-Jensen
- Kristian Hveem
- Tõnu Esko
- Maris Teder-Laving
- Alexandra Zhernakova
- Michael Camilleri
- Guy Boeckxstaens
- Peter J. Whorwell
- Robin Spiller
- Gil McVean
- Mauro D’Amato
- Luke Jostins
- Miles Parkes
Publication date
November 15, 2021
Summary:
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.
Published in
Nature Genetics
Volume and page numbers
Volume: 53 , p.1 -1
DOI
https://doi.org/10.1038/s41588-021-00950-8
ISSN
10614036
Subjects
Notes
Understanding Society used as a source of UK controls in this work
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