Association of depression with keratitis: A bidirectional 2-sample Mendelian randomization study

Observational studies suggest a potential link between depression and keratitis, but the causal relationship is unclear due to confounding. We used Mendelian randomization (MR) to examine the bidirectional causality between them. A bidirectional 2-sample MR analysis was performed using publicly available summary-level data from genome-wide association studies (GWAS) for depression and keratitis. The primary analytical method was the inverse-variance weighted (IVW) approach using a random-effects model. To ensure robustness of the findings, this was supplemented with 3 additional MR methods: weighted median, simple mode and weighted mode. Several sensitivity analyses were conducted, including Cochran Q test to assess heterogeneity, the MR-Egger intercept test to detect horizontal pleiotropy, and leave-one-out analysis to determine the influence of individual genetic variants. The IVW analysis showed a significant positive causal effect of depression on keratitis risk (odds ratio: 1.173; 95% confidence interval: 1.031-1.333; P = .015). Supplementary MR methods had consistent effect directions. Sensitivity analyses supported the primary result, showing no significant heterogeneity (Cochran Q = 19.194, P = .509) or horizontal pleiotropy (MR-Egger intercept = 0.011, P = .433). Leave-one-out analysis confirmed no single instrumental variable drove the causal estimate. Reverse MR analysis found no causal effect of keratitis on depression (P > .05). Our findings support a unidirectional causal relationship, with depression conferring an increased risk of keratitis but no evidence for a reverse causal effect. These results highlight the importance of psychiatric assessment in the management of patients with keratitis and imply shared underlying mechanisms that merit further investigation.