Genetics of irritable bowel syndrome and gastrointestinal complaints

Irritable bowel syndrome (IBS) affects 15% of people worldwide, is a leading cause of work absenteeism, and consumes 0.5% of the healthcare annual budget [PMID 24523597]. IBS symptoms include abdominal pain and bloating, constipation (IBS-C), diarrhea (IBS-D) or mixed constipation and diarrhea (IBS-M). In the absence of organic disease, IBS consensus diagnosis follows the expert guidelines from the Board of the Rome Foundation (Rome criteria, which are often implemented through questionnaires in order to recapitulate IBS symptoms and classification) [PMID 16678553]. These represent valuable instruments in IBS clinical research and management of patients in specialized tertiary centers, though are seldom part of clinical routine, where IBS is still a diagnosis of exclusion. Etiology is unknown and likely heterogeneous, why no effective cure has been developed. 
 
A heritable component of IBS has been demonstrated in family and twin studies. Several studies indicated that family member of an individual with IBS is 2–3 times more likely to have IBS [reviewed in PMID 21333900]. In a nation-wide survey of the Swedish population, an increased risk was detected among first, second and third degree relatives of IBS probands [PMID 24694578]. However, gene-hunting efforts in IBS lead to identification only a few associated loci. One potential reason for that is the large heterogeneity of IBS. IBS is characterized by various symptoms, including opposite ones (such as diarrhea and constipation), in different individuals it can be associated with mental complaints and mood disorders, or with specific reactions to food. We have also recently reported massive changes in microbiota composition in IBS patients (PMID 30567928).