Causal association between cystatin C and diabetic retinopathy: A two-sample Mendelian randomization study

Area of Science:

• Genetics and Epidemiology
• Ophthalmology
• Nephrology

Background:

• Diabetic retinopathy (DR) is a leading cause of vision loss.
• Cystatin C, a marker of kidney function, has been linked to DR, but causality is unclear.

Purpose of the Study:

• To investigate the causal relationship between cystatin C levels and different stages of diabetic retinopathy using Mendelian randomization (MR).

Main Methods:

• Utilized genome-wide association studies (GWAS) data for cystatin C and diabetic retinopathy (DR, PDR, SNPBDR).
• Employed various MR methods including Inverse Variance Weighting (IVW), MR-Egger, MR-PRESSO, and cML-MA.
• Conducted multivariable MR analysis to assess independent causal effects and reverse MR analysis.

Main Results:

• A significant causal relationship was observed between cystatin C levels and diabetic retinopathy, PDR, and SNPBDR.
• Results were consistent across multiple MR methods, with adjustments for outliers.
• Reverse MR suggested a potential influence of SNPBDR on cystatin C levels.

Conclusions:

• Mendelian randomization analysis supports a causal role of cystatin C in the development of diabetic retinopathy.
• Findings provide novel evidence for cystatin C as a potential therapeutic target for DR management.