The role of genetics in IBS

Abstract

Irritable bowel syndrome (IBS) is a common disorder that has been shown to aggregate in families and to affect multiple generations, but not in a manner consistent with a major Mendelian effect. Relatives of an individual with IBS are 2 to 3 times as likely to have IBS, with both genders being affected. To date, more than 100 genetic variants in more than 60 genes from various pathways have been studied in a number of candidate gene studies, with several positive associations reported. These findings suggest that there may be distinct, as well as shared, molecular underpinnings for IBS and its subtypes.

Figure 1

Gene-environment paradigm in IBS development. A gene-environment paradigm supports the importance of both genes and environment in the development of IBS for both familial and sporadic IBS. A number of combinations of individual genetic and environmental risk factors are possible, with each specific combination resulting in specific alterations in gastrointestinal motor and sensory function, and ultimately symptom presentation and the final clinical phenotype.

Figure 2

Familial aggregation of IBS. Fifty percent of cases with IBS will have at least one other family member with IBS, but the overall proportion of first-degree relatives with IBS is 25%. Overall, case-relatives are two to three times as likely to have IBS than control-relatives.

Figure 3

Estimated genetic liability and heritability in IBS twin studies. Five twin studies have evaluated the concordance of IBS between twin pairs. Genetic liability of IBS has been estimated to range between 1–20% and heritability estimates in the best fit model ranged between 0–57%.

Figure 4

Summary of positive gene associations, by IBS type and subtype. Positive gene associations that were shown in Table 1 are summarized by IBS phenotype. Some genetic associations are unique to specific IBS types and subtypes, where others were shown to overlap between IBS subtypes.