| Title: | Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disorders |
| Journal: | Nature Genetics |
| Published: | 5 Nov 2021 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/34741163/ |
| DOI: | https://doi.org/10.1038/s41588-021-00950-8 |
| URL: | https://www.nature.com/articles/s41588-021-00950-8.pdf |
| Citations: | 127 (98 in last 2 years) as of 8 Aug 2024 |
Publication 4996
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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 > 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.</p>
29 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
Enabling scientific discoveries that improve human health