Causal effects of psychiatric traits on the risk of urolithiasis in European and East Asian population: a Mendelian randomization analysis

Abstract

It has been reported in observation studies that psychiatric traits increase the risk of urolithiasis, but the causal association between them remains to be systematically reveal. Thus, this study aims to estimate the causal effect of psychiatric traits on urinary stones, utilizing Mendelian randomization (MR) analyses. In the study, we collected data of eight psychiatric traits from summary-level genome-wide association studies (GWAS), including attention deficit hyperactivity disorder, bipolar disorder, major depressive disorder (MDD), schizophrenia, insomnia, mood swing, anxiety and neuroticism. FinnGen consortium and BioBank Japan provided the GWAS data of urolithiasis. Three MR methodswere used in the study, in which inverse variance-weighted was employed as the primary analytic tool of causal reference. Furthermore, a meta-analysis combining the results from FinnGen and BioBank Japan was performed. In FinnGen, inverse variance-weighted analysis revealed that mood swing (p = 0.023, odds ratio (OR): 2.272, 95% confidence interval (CI): 1.122–4.600), neuroticism (p = 0.032, OR: 1.086, 95% CI: 1.007–1.171) and MDD (p = 0.014, OR: 1.259, 95% CI: 1.047–1.515) significantly increased the risk of urolithiasis, while schizophrenia (p = 0.026, OR: 0.944, 95% CI: 0.897–0.993) negatively associated with urolithiasis. In BioBank Japan, mood swing (p = 0.015, OR: 3.397, 95% CI: 1.273–9.062), neuroticism (p = 0.041, OR: 1.111, 95% CI: 1.004–1.228) and MDD (p = 0.006, OR: 1.435, 95% CI: 1.107–1.861) were found to have significant causality with urolithiasis. Combining meta-analysis revealed that mood swing (p = 0.001, OR: 2.606, 95% CI: 1.470–4.620), neuroticism (p = 0.003, OR: 1.095, 95% CI: 1.031–1.163) and MDD (p = 0.0003, OR: 1.316, 95% CI: 1.132–1.530) significantly increase the risk of urinary calculus, while schizophrenia (p = 0.04, OR: 0.959, 95% CI: 0.922–0.997) decrease the risk of urinary stones formation to our surprise.

Keywords

• psychiatric traits
• mendelian randomization
• urolithiasis
• causality