Bidirectional relationships between mental health problems and urinary incontinence in women: a two-sample Mendelian randomization analysis

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Abstract
Objective: Comorbidity between urinary incontinence (UI) and affective disorders, including anxiety and depression, is well established in cross-sectional studies and prospective bidirectional associations have also been reported. It is, however, unclear whether these associations are causal. We applied two-sample Mendelian randomization (MR) analysis to examine if there are causal bidirectional relationships between UI and anxiety, depression, and neuroticism in women. Materials and methods: We used summary level data from independent genome-wide association studies (GWAS) to estimate the bidirectional causal effects of UI and its subtypes (stress urinary incontinence (SUI), urgency urinary incontinence (UUI), and mixed urinary incontinence (MUI), n=10,931) on anxiety (n=83,566), depression (n=1,035,760), broad depression phenotype (n=500,199) and neuroticism (n=329,821). Results: We found little evidence of causal effects in either direction, except for weak evidence suggesting that UUI may reduce the risk of depression (causal odds ratio (OR) for depression: 0.99, 95% confidence interval (95%CI) 0.98-1.00; OR for broad depression 0.98, 95%CI 0.96-1.00). However, the direction of effect estimates did not consistently align across sensitivity analysis methods and the magnitude of this effect could be considered negligible. Conclusion: Our study provided little evidence for causal bidirectional relationships between UI and anxiety, depression and neuroticism. This study highlights the need for further GWAS of UI (including different subtypes) with larger sample sizes. Highlights: There was little evidence for causal bidirectional relationships between urinary incontinence (UI) and anxiety, depression, and neuroticism. Study limitations, including low statistical power, UI phenotype definition, and genetic instrument strength, need to be considered when interpreting the findings. Larger and more comprehensive GWAS of UI (including subtypes) are needed before ruling out causal relationships between UI and mental health.

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