Irritable bowel syndrome (IBS) affects 4-11% of the population during their lifetime and its development is influenced by many factors related to genetics and environment. A study led by the Vall d'Hebron Research Institute (VHIR) has investigated its genetic basis and has identified 38 new gene variants associated with the syndrome. Among the genes found are some involved in other digestive disorders and also in psychiatric disorders, such as depression, anxiety or neuroticism. The work, published in Journal of Translational Medicine, has been led by the Psychiatry, Mental Health and Addictions group of VHIR with the Physiology and Digestive Pathophysiology group of VHIR, the CIBER of Mental Health (CIBERSAM) and the CIBER of Liver and Digestive Diseases (CIBEREHD) and is part of the European project DISCOvERIE.

IBS is a gastrointestinal disorder characterized by abdominal pain, changes in bowel rhythm and food intolerances. "It is a complex disease to study, as there are many factors related to the development and patients usually have very diverse symptomatology", explains Dr. Javier Santos, assistant of the Digestive System Service at Vall d'Hebron University Hospital, researcher of the Physiology and Digestive Pathophysiology group at VHIR and CIBEREHD researcher. "For this reason, we need a large amount of information to be able to understand the genetic basis of this disorder, so far largely unknown", he says.

In addition, in 28-40% of cases, patients with IBS also present psychiatric disorders, especially anxiety and depression. This association is related to the brain-gut axis, which connects the brain with the digestive system, but the genetic basis that links the different disorders is unknown. In this work, data from previous studies with samples of more than 880,000 people are analyzed, including healthy people and people with IBS, depression or anxiety or high scores in neuroticism (a personality trait associated with a propensity to experience negative emotions). "Until now, 6 gene variants related to this syndrome were known. This large amount of data has allowed us to identify 38 new variants involved in IBS", highlights Dr. María Soler Artigas, researcher of the Psychiatry, Mental Health and Addictions group at VHIR and CIBERSAM.

Among the genetic variants described are genes involved in brain development, psychiatric disorders and digestive disorders. "The fact that we confirm that there are genes related to the digestive system reinforces the biological entity of irritable bowel syndrome as a digestive disease, beyond the psychiatric symptoms that are often associated with it", says Dr. Silvia Alemany, principal investigator of the Psychiatry, Mental Health and Addictions group at VHIR.

A shared genetic basis between IBS and psychiatric disorders
The study also provides insight into the relationship between psychiatric disorders and IBS. Of the total number of variants associated with IBS, 27 of them were also found to be related to at least one of the disorders under study. "The finding of a shared genetic basis explains the high frequency of patients with both disorders. Knowing the comorbidity between the different disorders and the genetics associated with the two is important to make a better follow-up of patients affected by these pathologies", explains Dr. Josep Antoni Ramos Quiroga, head of the Psychiatry Service at Vall d'Hebron University Hospital and of the Psychiatry, Mental Health and Addictions group at VHIR and CIBERSAM researcher.

Finally, the research team shed light on the causal relationship between psychiatric disorders and IBS. In line with previous studies, genetic susceptibility for IBS is associated with a higher probability of suffering depression and neuroticism and vice versa. These results point to a bidirectional relationship between these disorders. However, in the case of anxiety, the results indicate that genetic susceptibility to irritable bowel increases the probability of suffering from anxiety, but not the other way around.

DISCOvERIE: a project to understand the relationship between irritable bowel syndrome and psychiatric disorders

The study is part of the European macroproject DISCOvERIE (Development, diagnosis and prevention of gender-related somatic diseases and mental disorders in irritable bowel syndrome in Europe), which involves 19 health institutions, universities, research centers and companies and is coordinated by VHIR.

The aim of DISCOvERIE is to understand the relationship between irritable bowel syndrome and mental disorders such as anxiety or depression, as well as with other diseases such as fibromyalgia or chronic fatigue syndrome and their risk factors. Taking into account that associated disorders or comorbidities influence the risk factors for irritable bowel syndrome, it is important to understand the relationship between irritable bowel syndrome and mental disorders such as anxiety or depression.

This document is an output of DISCOvERIE, a project grant (Grant Agreement nº: 848228) funded with 6 million euros under H2020 Research Programme of the European Commission and will last for 5 years (2020-2024). The content of this document represents the views of the author only and is his/her sole responsibility; it cannot be considered to reflect the views of the European Commission or any other body of the European Union. The European Commission do not accept any responsibility for use that may be made of the information it contains.