Genetic variants could link anxiety and irritable bowel syndrome

Irritable bowel syndrome (IBS) and mood and anxiety disorders are genetically linked, with brain-gut pathways playing a key role.

IBS is a common condition affecting the gut, however, the causes of the disease are not well understood. An international team of scientists coordinated by researchers in the UK and Spain used a genome-wide association study to assess genetic susceptibility to IBS. Using cases from the UK Biobank and the Bellygenes initiative, 53,400 participants with IBS were compared to 433,201 participants without IBS, all of European descent. The results were replicated in a 23andMe panel using 205,252 subjects with IBS and 1,384,055 subjects without IBS.

'Although IBS occurs more frequently in those who are prone to anxiety, we don't believe that one causes the other – our study shows these conditions have shared genetic origins, with the affected genes possibly leading to physical changes in brain or nerve cells that in turn cause symptoms in the brain and symptoms in the gut' said Professor Miles Parkes, the study co-senior investigator and consultant gastroenterologist from the University of Cambridge.

The study published in Nature Genetics found loci more common in people with IBS than controls on six genes: NCAM1, CADM2, PHF2/FAM120A, DOCK9, CKAP2/TPTE2P3 and BAG6. The first four are known to be linked with mood and anxiety disorders. In addition, there were strong links between the risk of IBS and neuroticism, depression and insomnia. These genes are understood to be expressed in the brain tissue and the nerves that connect the brain to the gut, instead of the gut itself.

Previous attempts to understand the role of genes passed on from one family member to another play in a person's risk of developing IBS have been inconclusive. This study found that the impact of having the implicated gene variants on the risk of developing IBS was small, and that other factors including diet, stress, antibiotic use during childhood and learned behaviours all had a greater impact on risk. The authors also noted that these factors can be shared within families.

Co-senior investigator Dr Luke Jostins from the University Oxford said, 'We anticipate that future research will build on our discoveries, both by investigating the target genes identified and exploring the shared genetic risk across conditions to improve understanding of the disordered brain-gut interactions which characterise IBS'.

Current IBS treatments include dietary interventions to psychoactive medicines, which are not particularly effective. Behavioural therapies are more effective though not widely available. Lead author Chris Eijsbouts from the University of Oxford commented, 'Even genetic changes that have only subtle effects on IBS can provide clues about pathways to target therapeutically. Unlike the individual genetic changes themselves, drugs targeting the pathways they tell us about may have a considerable impact on the condition, as we know from other disease areas'.