Causal association between cataract and psychiatric disorders: A bidirectional 2-sample Mendelian randomization study

Abstract

This study aimed to investigate the genetic causality between cataract (senile and other types) and psychiatric disorders using Mendelian randomization (MR). We performed a bidirectional 2-sample MR analysis using genome-wide association studies summary data. Primary analysis employed inverse-variance weighted, MR-Egger, weighted median, and weighted mode methods. Sensitivity analyses included Cochran Q, MR-pleiotropy residual sum and outlier, MR-Egger intercept, and leave-one-out tests to assess heterogeneity and pleiotropy. Forward MR analysis revealed a suggestive causal effect of other cataract on anxiety (inverse-variance weighted odds ratio [OR] = 0.99, 95% confidence interval: 0.98–1.00, P = .043), though unsupported by other methods. MR-Egger and weighted median suggested potential associations between other cataract and bipolar disorder (P < .05). No significant links were found between senile cataract and psychiatric disorders. Reverse MR analysis showed no consistent causal effects, except for anxiety disorder on other cataract (MR-Egger OR = 8.04, P = .040; weighted median OR = 2.99, P = .047). Sensitivity analyses confirmed robustness despite heterogeneity. This study provides evidence of a potential causal relationship between other cataract and anxiety, though findings were method-dependent. No significant associations were observed for senile cataract or most psychiatric disorders.