Genetically predicted retinal vascular occlusion in relation to cardiovascular diseases: A bidirectional two‐sample Mendelian randomization analysis

Increasing evidence implicates retinal vascular occlusions as a susceptibility factor for cardiovascular diseases (CVDs), whereas inconsistent results on the relationship were reported in previous observational studies. This research using a bidirectional two-sample Mendelian randomization (MR) analysis aimed to investigate the potential association between genetically determined central/branch retinal artery and retinal vein occlusions (CRAO/BRAO/RVO) and the risk of CVD.Summary statistics of retinal vascular occlusions from the largest available genome-wide association study of European descent were used to investigate their relationship with CVDs, and vice versa. Primary analyses were conducted using the common inverse-variance weighted approach. Several complementary sensitivity analyses were performed to verify the reliability of our results.Inverse variance weighted method showed suggestive effects of genetically determined RVO on ischemic stroke (IS) (odds ratio [OR] = 1.021, 95% confidence [CI] = 1.004-1.037, p = 0.012), a genetic liability to CRAO increased the risk of myocardial infarction (MI) (OR = 1.014, 95% CI = 1.006-1.023, p = 7.0 × 10-4). In addition, genetic predisposition to BRAO had a positive effect on stroke (OR = 1.008, 95% CI = 1.002-1.013, p = 0.011), IS (OR = 1.007, 95% CI = 1.001-1.014, p = 0.022), and cardioembolic stroke (CES) (OR = 1.018, 95% CI = 1.006-1.031, p = 0.004). The point estimates from sensitivity analyses were in the same direction. Reverse MR analyses found no significant evidence for the effect of CVDs on retinal vascular occlusions.Our MR study provides potential evidence that retinal vascular occlusions are causally linked to increased risk of CVDs including IS, MI, stroke, and CES. This supports the need for clinical CVD screening in individuals with retinal vascular occlusions. Further investigations are warranted to clarify the effects of CVDs on ocular comorbidities.