Polygenic risk score predicting susceptibility of female overactive bladder in the Han Chinese

Abstract Objective: Our study aims to explore the predictive potential of a polygenic risk score (PRS) in overactive bladder (OAB) as well as its impact on drug compliance. Materials and methods: This retrospective cohort study involved 29,812 female participants from Taichung Veterans General Hospital, enrolled in the Taiwan Precision Medicine Initiative (TPMI), and genotyped using the Affymetrix Genome-Wide TWB 2.0 SNP Array. PRS was determined using PGS002112 for depression, which included 748,601 single nucleotide polymorphisms. PRS scores were categorized into quartiles (Q1-Q4) and their association with OAB incidence was analyzed using logistic regression model, including overactive bladder (ICD-9-CM code 596.51), urinary incontinence (ICD-9-CM code 788.3) and frequency (ICD-9-CM code 788.4). Results: Among 29,812 female participants, 2,583 were diagnosed with OAB. Risk of non-neurogenic female low urinary tract was higher in the fourth quartile (Q4) than the first quartile (Q1) (OR=1.16, 95% CI=1.03-1.30, p=0.016). In addition, the PGS002112 Q4 group displayed a heightened prevalence of depression and anxiety. Our results reveal that PRS effectively predicts the occurrence of depression (Q4 vs. Q1, OR=1.21, 95% CI=1.03-1.43, p=0.021) and anxiety (Q4 vs. Q1, OR=1.25, 95% CI=1.12-1.38, p<0.001). However, the PRS score did not correlate with drug compliance, including antimuscarinic (p=0.509), beta-3 agonist (p=0.411), or both types of drugs (p=0.352). Conclusions and relevance: In this hospital-based cohort, a higher PRS was associated with the susceptibility to OAB in female Han Chinese, as well with susceptibility to depression and anxiety. Prospective large-scale study with longer follow-up would be needed to validate our result.