Genetics of OAB syndrome

Introduction & Objectives

The underlying pathophysiological mechanisms of Overactive Bladder (OAB) syndrome and the distinctions between OAB-dry and OAB-wet subtypes remain inadequately elucidated. Twin analyses offer a means to unravel the etiological origins of a condition while quantifying the degree of shared genetic and environmental influences. In this investigation, we employed a classical twin model to assess the extent of genetic and environmental contributions to OAB syndrome and to ascertain whether these factors exert a similar influence on both OAB-dry and OAB-wet subtypes.

Materials & Methods

A prospective survey was conducted using a large UK twin database. 5092 participants completed the International Consultation on Incontinence Questionnaire (ICIQ) short form for urinary incontinence (UI-SF) and the ICIQ for Overactive Bladder (OAB). Individuals with a history of recurrent urinary tract infections, neurological disorders, or stress urinary incontinence were excluded from the study. Responses to both questionnaires were carefully reviewed, and incongruent responses were excluded listwise.

Structural equation modelling was employed to delineate the genetic and environmental contributors to variance. Model comparisons were carried out utilizing Akaike’s information criterion. Univariate analyses were performed for the overall assessment of OAB syndrome using the ICIQ-OAB score, and for those with OAB-wet using ICIQ-UI SF scores. Bivariate analysis was conducted to compare OAB-dry and OAB-wet subtypes.

Results

3540 participants were included in this study, with a median age of 64 years, and 83% of the participants were female. Mean OAB score was 2.45 ± 2.09, and 25% of subjects reported urge urinary incontinence. In univariate analysis, the most fitting models revealed heritability estimates of 41% for OAB syndrome and 37% for OAB-wet. Non-shared environmental factors accounted for 59% of the variance in OAB syndrome and 63% in OAB-wet, while shared environmental factors were not found to be significant. Bivariate models were employed to evaluate the shared factors between these syndromes. Bivariate heritability between OAB-dry and OAB-wet was 57%, indicating the proportion of variance between the two conditions explained by genetic factors. Non-shared environmental covariance contributed 43%. Genetic and environmental correlations were examined to determine the extent to which the same genetic and environmental factors influence both conditions. The genetic correlation was found to be 48%, while the shared environmental correlation was 26%.

Conclusions

This study has shown heritability for both OAB syndrome overall and OAB-wet to be approximately 40%, with the remaining variance attributable to non-shared environmental factors. Notably, only 48% of genetic factors and 26% of environmental influences were found to be common between OAB-dry and OAB-wet, indicating distinct pathophysiological mechanisms underlying these two conditions.