Insights into modifiable risk factors of retinal vascular occlusion: A Mendelian randomization study

Understanding the etiological risk factors for retinal vascular occlusion (RVO) is critical for prevention and treatment. While the effects of cardiovascular events, hypertension, glaucoma, obesity and glycemic risk factors on RVO are still controversial. This study employed two-sample Mendelian randomization (MR) analysis to investigate these causal risk factors. Single-nucleotide polymorphisms (SNPs) were used as instrumental variables (IVs). Genetic instruments for hypertension, glaucoma, obesity, cardiovascular events and glycemic risk factors were obtained from published genome-wide association studies (GWASs). Summary-level data for RVO and hypertension were obtained from the FinnGen consortium. MR analysis primarily utilized the inverse variance weighted (IVW) method, with MR-Egger and weighted median as supplementary approaches. Multivariable MR (MVMR) adjusting for hypertension or glaucoma of RVO were conducted. Heterogeneity was assessed using Cochrane's Q test and I2, while MR-Egger intercept and MR-PRESSO tested horizontal pleiotropy. All MR analyses were performed within R software (4.1.3) using the R packages "TwoSampleMR" and "MR-PRESSO." Genetic instruments for hypertension and glaucoma were significantly associated with RVO risk. A one-standard deviation (SD) increase in hypertension was associated with a higher risk of RVO [OR = 1.577, 95% CI = (1.342, 1.854), P < .001], while a one-SD increase in the log odds of genetically predicted glaucoma was associated with a higher risk of RVO [OR = 1.24, 95% CI = (1.115, 1.379), P < .001]. Meanwhile, hypertension and glaucoma were still significant in multivariable MR. There was not sufficient evidence to suggest cardiovascular events and obesity were associated with RVO risk. This MR study provided genetic evidence supporting that hypertension and glaucoma were causally associated with the risk of RVO. It may help guide clinical decisions in the management of RVO patients with hypertension and glaucoma.