Background: Previous observational studies have indicated a correlation between metabolic syndrome and cataract. However, the causal relationship remained unclear. Objective: This study aimed to elucidate the causal impact of metabolic syndrome and its components on cataract and to explore the mediating role of C-reactive protein (CRP). Methods: Summary-level data for metabolic syndrome, its components (waist circumference, hypertension, fasting blood glucose, triglyceride, and high-density lipoprotein cholesterol), cataract, and CRP were derived from publicly available genome-wide association studies. Univariate Mendelian randomization (UVMR) analyses were conducted to investigate the total causal relationship between metabolic syndrome and its components on cataract. In addition, multivariate MR (MVMR) was utilized to evaluate the direct effect of metabolic syndrome and its components after adjusting for aging, smoking, drinking and physical activity. To further investigate the potential mechanisms, CRP was employed as a mediating variable. Two-step MR analysis was applied to assess the mediating role of CRP. Results: The results of UVMR suggested that genetically predicted metabolic syndrome [(OR (95%CI): 1.206(1.125, 1.292), P < 0.001], waist circumference [(OR (95%CI): 1.118(1.045, 1.196), P = 0.001] and hypertension [(OR (95%CI): 2.075(1.277, 3.370), P = 0.003] were associated with an increased risk of cataract. However, fasting blood glucose [(OR (95% CI): 1.038(0.915, 1.177), P = 0.567], triglyceride [(OR (95%CI): 0.986(0.940, 1.035), P = 0.703] and high-density lipoprotein cholesterol [(OR (95%CI): 0.992(0.951, 1.035)), P = 0.683] were not associated with an increased risk of cataract. MVMR analysis indicated that metabolic syndrome [(OR (95%CI): 1.099(1.017, 1.186), P = 0.017] and hypertension [(OR (95%CI): 1.731(1.060, 2.832), P = 0.029] still had a causal effect on increased risk of cataract after adjusting for aging, smoking, drinking and physical activity. In two-step MR analysis revealed CRP was a mediator between metabolic syndrome and cataract with a mediated proportion of 16.2% (95%CI: 10.9%, 21.6%). No mediating effect of CRP between metabolic syndrome components and cataract was found. Conclusions: This study provides evidence that metabolic syndrome is a risk factor for cataract, with hypertension likely playing a major role. Furthermore, CRP has a mediating effect between metabolic syndrome and cataract.

Metabolic Syndrome, Cataract, C-reactive Protein, Mendelian Randomization