Association of Polygenic Risk Scores for Depression, Anxiety, and Neuroticism with Lower Urinary Tract Symptoms Among Women

Eur Urol. 2025 Oct 10:S0302-2838(25)04704-9. doi: 10.1016/j.eururo.2025.09.4154. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Observational studies have found that depression, anxiety, and neuroticism are prospectively associated with lower urinary tract symptoms (LUTS) among women, but are limited by confounding and measurement errors. We examined whether genetic liability for these psychiatric traits is associated with LUTS among women.

METHODS: Participants were from the mothers cohort of the Avon Longitudinal Study of Parents and Children (ALSPAC). Polygenic risk scores (PRSs) for depression, anxiety, and neuroticism were calculated using summary data from genome-wide association studies. LUTS were assessed using validated questionnaires at two time points: 2002-2004 (n = 4758; median age 40 yr, interquartile range [IQR] 37-43) and 2011-2012 (n = 3026; median age 50 yr, IQR 47-53). Separate logistic regression models, adjusted for age and population structure, were fitted to examine the association of each PRS with each LUTS.

KEY FINDINGS AND LIMITATIONS: The neuroticism PRS was associated with nocturia at both time points [odds ratio and 95% confidence intervals=1.24 (1.10,1.40) and 1.21 (1.07,1.37)], and with any urinary incontinence (UI), any urgency, and mixed UI (2002-04) [1.14 (1.05,1.23), 1.12 (1.02,1.23), and 1.23 (1.07,1.43), respectively]. The depression PRS was associated with nocturia [OR 1.33, 95% CI 1.17-1.50) and 1.24 (1.09,1.40)] and any UI [1.09 (1.01,1.18); 1.11 (1.02,1.20)] at both time points, and with any urgency (2011-12) [1.13 (1.03,1.24)]. The anxiety PRS was associated with mixed UI (2002-04) [1.20 (1.03,1.39)]. Limitations include PRS not capturing all genetic liability, potential pleiotropic effects, and restriction of the cohort to parous women of predominantly European ancestry.

CONCLUSIONS AND CLINICAL IMPLICATIONS: Genetic liability for depression, anxiety, and neuroticism is associated with higher risk of LUTS among women. This finding indicates a potential shared aetiology or a possible contribution of mental health problems in the development of LUTS.

PMID:41076405 | DOI:10.1016/j.eururo.2025.09.4154