Mendelian Randomization Analyses Support Causal Relationships Between Psychiatric Disorders and Risk of Urinary Tract Infections

Abstract

Observational studies have identified a significant co-morbidity between urinary tract infections (UTIs) and psychiatric disorders, yet the causal relationship remains uncertain. We conducted a bidirectional Mendelian randomization (MR) analysis to evaluate the causal relationship between psychiatric disorders (schizophrenia [SC], bipolar disorder [BD], major depressive disorder [MDD], autism spectrum disorder [ASD], attention-deficit/hyperactivity disorder [ADHD], obsessive-compulsive disorder [OCD], anorexia nervosa [AN]) and UTIs using data from the Psychiatric Genomics Consortium and UK Biobank. To account for potential confounding factors and investigate the independent effects of multiple psychiatric disorders, we further employed multivariable Mendelian randomization (MVMR). Inverse variance weighted analysis demonstrated that genetic susceptibilities of MDD and ASD increased UTI risk with odds ratios (ORs) of 1.31 (95% CI: 1.15–1.48, p < .001) and 1.08 (95% CI: 1.03–1.15, p = .004), respectively. UTIs were associated with a slight increase in the risk of MDD, evidenced by an OR of 1.061 (95% CI: 1.01–1.12, p = .019). Multivariate MR analysis revealed that MDD, after adjusting for type 2 diabetes mellitus and urinary stones, increased UTI risk (OR = 1.25, 95% CI: 1.08–1.45, p = .002), with smoking mediating 13.6% (p = .006) of MDD’s effect on UTIs. Our study establishes a causal relationship between psychiatric disorders and UTIs, identifying smoking as a mediator. These findings provide valuable guidance for clinicians to develop effective prevention and management strategies for patients with coexisting mental disorders and UTIs.