Does uveitis increase the risk of age-related wet macular degeneration? A Mendelian randomization study

AIM: To use two-sample Mendelian randomization (MR) method to study uveitis causal association with wet age-related macular degeneration (wAMD) risk from the genetic level. METHODS: Two-sample MR analysis was used to assess the causal role of uveitis on wAMD risk, using the 8 genetic variants associated strongly with uveitis as instrumental variables. Besides, eight MR methods [inverse variance weighted (IVW), weighted median, MR-Egger regression, weighted mode, simple mode, robust adjusted profile score (RAPS), contamination inverse-variance weighted method, and debiased inverse-variance weighted method] were used to get the whole causal estimate for multiple instrumental single nucleotide polymorphism (SNPs). The MR analysis was based on Europeans. RESULTS: Uveitis was related to a higher risk of wAMD [odds ratio (OR): 1.08, 95% confidence interval (CI) 1.03–1.12; P=1.03×10-3] with the IVW method. No heterogeneity and directional pleiotropy were detected. On the contrary, no significant results were detected in reverse MR analysis. CONCLUSION: Uveitis is related to an increased risk of wAMD. Due to the high blindness rate of wAMD, understanding and controlling the risk factors of AMD is of great significance for reducing its incidence and early diagnosis and treatment.