Large-scale genetic study reveals new clues about common origins of irritable bowel syndrome and mental health disorders

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IBS is a common condition around the world, affecting about 1 in 10 people and causing a wide range of symptoms, including abdominal pain, bloating, and intestinal dysfunction that can dramatically affect people’s lives. The diagnosis is usually made after examining other possible conditions (such as Crohn’s disease or bowel cancer), with clinical tests returning to “normal”. The disease is often familial and is also more common in people prone to anxiety. The causes of IBS are not well understood, but an international team of researchers has now identified several genes that provide clues to the origins of IBS.

The research team, comprising over 40 institutions and coordinated by scientists in the UK and Spain, examined genetic data from 40,548 people with IBS from UK Biobank and 12,852 from the Bellygenes initiative (a global study to identify genes linked to IBS) and compared them to 433,201 people without IBS (controls), focusing on individuals of European descent. The results were repeated with anonymized data from genomics company 23andMe Inc., provided by clients who consented to the research, comparing 205,252 people with IBS to 1,384,055 controls.

The results showed that overall, the heritability of IBS (how well your genes influence the likelihood of developing a particular disease) is quite low, indicating the importance of environmental factors such as diet, stress and behavioral patterns that can also be shared in the family environment.

However, 6 genetic differences (influencing the NCAM1, CADM2, PHF2 / FAM120A, DOCK9, CKAP2 / TPTE2P3 and BAG6 genes) were more common in people with IBS than in controls. As the symptoms of IBS affect the gut and gut, one would expect genes associated with an increased risk of IBS to be expressed there – but that’s not what the researchers found. Instead, most of the altered genes seem to have clearer roles in the brain and perhaps the nerves that supply the gut, rather than the gut itself.

Researchers also looked for an overlap between susceptibility to IBS and other physical and mental health problems. They found that the same genetic makeup that puts people at increased risk for IBS also increases the risk of common mood and anxiety disorders such as anxiety, depression, and neurosis, as well as insomnia. . However, the researchers stress that this does not mean that the anxiety causes symptoms of IBS or vice versa.

Professor Miles Parkes, senior researcher and consultant gastroenterologist for the study, University of Cambridge, explained: “IBS is a common problem and its symptoms are real and debilitating. Although IBS occurs more frequently in those who are prone to anxiety, we don’t believe that one causes the other – our study shows that these conditions have common genetic origins, with affected genes that can lead to physical changes. in the brain or nerve cells which in turn cause symptoms in the brain and symptoms in the gut.

The study also found that people with both IBS and anxiety were more likely to have been frequently treated with antibiotics during childhood. The study authors hypothesize that repeated use of antibiotics during childhood could increase the risk of IBS (and possibly anxiety) by altering the “normal” gut flora (healthy bacteria that live normally in the gut) which in turn influence nerve cell development and mood.

Current treatments for IBS vary widely and include dietary changes, prescription drugs targeting the gut or brain, or behavioral interventions. Lead author Chris Eijsbouts of the University of Oxford suggests that the discovery of genes that contribute to IBS may help in the development of new long-term treatments. He said: “Even genetic changes that have only subtle effects on IBS can provide clues as to which pathways to target therapeutically. Unlike individual genetic modifications themselves, drugs targeting the pathways they tell us about can have a dramatic impact on disease, as we know from other disease areas.

Co-principal investigator Dr Luke Jostins of the University of Oxford said: “We anticipate that future research will build on our findings, both by studying the identified target genes and by exploring the genetic risk. shared between conditions to improve understanding of disordered brain and gut interactions. that characterize IBS.

“The IBS presents a remarkable challenge for genetic studies. These first results are long overdue and finally tell us that this type of research is worth it, ”added Professor Ikerbasque Mauro D’Amato from CIC bioGUNE, co-principal investigator and coordinator of the Bellygenes initiative.

This research received funding and support from the National Institute for Health Research (NIHR) Biomedical Research Centers in Cambridge, Oxford, Nottingham and Manchester. Additional funding and support has been received from the Wellcome Trust, the Li Ka Shing Foundation and the Kennedy Trust for Rheumatology Research in the UK, and the Spanish Ministry of Economy and Competitiveness (Instituto Salud Carlos III), of the Department of Health of the Basque government and the Swedish Research Council (Vetenskapsradet).

Reference

Eijsbouts, C et al. Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights genetic pathways shared with mood and anxiety disorders. Genetics of nature; November 5, 2021; DOI: 10.1038 / s41588-021-00950-8

Adapted from a press release from the National Institute for Health Research


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