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.
Zhang et al. (Fri,) studied this question.