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.

Original languageEnglish
Pages (from-to)1543-1552
Number of pages10
JournalNature Genetics
Issue number11
Publication statusPublished - 5 Nov 2021


  • Aged
  • Anxiety Disorders/genetics
  • CD56 Antigen/genetics
  • Cell Adhesion Molecules/genetics
  • Cytoskeletal Proteins/genetics
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Guanine Nucleotide Exchange Factors/genetics
  • Homeodomain Proteins/genetics
  • Humans
  • Irritable Bowel Syndrome/epidemiology
  • Male
  • Middle Aged
  • Molecular Chaperones/genetics
  • Mood Disorders/genetics
  • Polymorphism, Single Nucleotide
  • United Kingdom/epidemiology


Dive into the research topics of 'Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disorders'. Together they form a unique fingerprint.

Cite this