Independent causal effect of α, β, and γ crystallin on cataract: A Mendelian randomization study

OBJECTIVE: This study aimed to explore the independent causal relationship between three types of crystallin proteins (α, β, and γ) and risk of cataract, using single nucleotide polymorphisms (SNPs) as instrumental variables for α, β, γ crystallin through Mendelian randomization (MR) analysis. METHODS: Genetic instruments associated with α, β, γ crystallin levels and cataract were obtained from the IEU Open GWAS Project (GWAS IDs: prot-a-673, prot-a-674, prot-a-675, and ukb-d-20002_1278). Two-sample MR analyses were conducted using five different MR algorithms containing MR-Egger, inverse variance weighted (IVW), Weighted median, Simple mode, and MR-PRESSO. RESULTS: The MR analysis revealed a significant causal relationship between α crystallin level and the risk of cataract [odds ratio (OR)IVW = 0.9989, 95% CI 0.9978~0.9999; ORMR-PRESSO= 0.9988, 95% CI 0.9978~0.9999]. Conversely, no significant causal relationship was found between β or γ crystallin and the risk of cataract. CONCLUSION: The occurrence of cataract may be potentially linked to abnormal levels of α crystallin, suggesting that monitoring and managing these levels could be crucial in understanding and potentially mitigating the risk of cataract.