Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disorders

Publication type

Journal Article

Authors

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

Covered by over 20 media outlets

#547031


Related Publications

  • Anxiety link to irritable bowel syndrome seen in DNA – research

    1. Chris Eijsbouts
    2. Tenghao Zheng
    3. Nicholas A. Kennedy
    4. Ferdinando Bonfiglio
    5. Carl A. Anderson
    6. Loukas Moutsianas
    7. Joanne Holliday
    8. Jingchunzi Shi
    9. Suyash Shringarpure
    10. Alexandru-Ioan Voda
    11. Gianrico Farrugia
    12. Andre Franke
    13. Matthias Hübenthal
    14. Gonçalo Abecasis
    15. Matthew Zawistowski
    16. Anne Heidi Skogholt
    17. Eivind Ness-Jensen
    18. Kristian Hveem
    19. Tõnu Esko
    20. Maris Teder-Laving
    21. Alexandra Zhernakova
    22. Michael Camilleri
    23. Guy Boeckxstaens
    24. Peter J. Whorwell
    25. Robin Spiller
    26. Gil McVean
    27. Mauro D’Amato
    28. Luke Jostins
    29. Miles Parkes

    Media
    November 6, 2021

News

Latest findings, new research

Publications search

Search all research by subject and author

Podcasts

Researchers discuss their findings and what they mean for society

Projects

Background and context, methods and data, aims and outputs

Events

Conferences, seminars and workshops

Survey methodology

Specialist research, practice and study

Taking the long view

ISER's annual report

Themes

Key research themes and areas of interest