Correlation between diabetic retinopathy and diabetic nephropathy: a two-sample Mendelian randomization study

Area of Science:

• Genetics
• Epidemiology
• Ophthalmology
• Nephrology

Background:

• Diabetic retinopathy (DR) and diabetic nephropathy (DN) are common diabetes complications.
• Previous studies suggest an association, but causal links require further investigation.

Purpose of the Study:

• To investigate the causal relationship between diabetic retinopathy and diabetic nephropathy using a genetic approach.
• To assess if DR can serve as a non-invasive predictor for DN.

Main Methods:

• A two-sample Mendelian randomization study utilizing genetic variants.
• Selected 20 independent single nucleotide polymorphisms (SNPs) for DR from FinnGen.
• Obtained summary-level data for DN from GWAS, FinnGen, and CKDGen consortia.
• Employed Inverse Variance Weighted (IVW) as the primary analysis method.
• Conducted sensitivity analyses (Cochran's Q, MR-Egger, MR-PRESSO, leave-one-out) to ensure robustness.

Main Results:

• Genetically predicted DR showed a significant positive association with DN (OR=1.32; P=3.72E-11).
• Positive associations were also found for type 1 (OR=1.96; P=7.11E-11) and type 2 diabetes with renal complications (OR=1.26, P=3.58E-04).
• Both non-proliferative DR (OR=1.07, P=0.000396) and proliferative DR (OR=1.67, P=3.699068E-14) were significantly associated with DN.

Conclusions:

• This study provides strong genetic evidence supporting a causal link between diabetic retinopathy and diabetic nephropathy.
• Findings suggest that DR can be a valuable non-invasive biomarker for predicting the risk of DN.
• Results are consistent with clinical observations and robust across multiple sensitivity analyses.