Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. X:X | DOI: 10.5507/bp.2026.015

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

Xin Li1, Ling-Li Xu2, Jian Cheng3, 4, Qi-Di Hu2
1 Department of Ophthalmology, Puyang Second People's Hospital, Puyang 457000, Henan Province, China
2 Department of Ophthalmology, Wenzhou Medical University Ningbo Eye Hospital, Ningbo 315040, Zhejiang Province, China
3 Ningbo Clinical Research Center for Ophthalmology, Ningbo 315040, Zhejiang Province, China
4 Department of Ophthalmology, the Affiliated People's Hospital of Ningbo University, Ningbo 315040, Zhejiang Province, China

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.

Keywords: α crystallin, β crystallin, γ crystallin, cataract, Mendelian randomization

Received: March 10, 2025; Revised: May 20, 2026; Accepted: June 12, 2026; Prepublished online: July 15, 2026 

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