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

Rationale & objective: A causal relationship concerning diabetic retinopathy (DR) and diabetic nephropathy (DN) has been studied in many epidemiological observational studies. We conducted a two-sample mendelian randomization study from the perspective of genetics to assess these associations. Methods: 20 independent single nucleotide polymorphisms (SNPs) associated with diabetic retinopathy were selected from the FinnGen consortium. Summary-level data for diabetic nephropathy were obtained from the publicly available genome-wide association studies (GWAS) database, FinnGen and CKDGen consortium. Inverse variance weighted (IVW) was selected as the primary analysis. MR-Egger, weighted median (WM), simple mode and weighted mode were used as complementary methods to examine causality. Additionally, sensitivity analyses including Cochran's Q test, MR-Egger, MR-Pleiotropy Residual Sum and Outlier (MR-PRESSO), and leave-one-out analyses were conducted to guarantee the accuracy and robustness of our MR analysis. Results: Our current study demonstrated positive associations of genetically predicted diabetic retinopathy with diabetic nephropathy (OR=1.32; P=3.72E-11), type 1 diabetes with renal complications (OR=1.96; P= 7.11E-11), and type 2 diabetes with renal complications (OR=1.26, P=3.58E-04). Further subtype analysis and multivariate mendelian randomization (MVMR) also reached the same conclusion. A significant casualty with DN was demonstrated both in non-proliferative DR (OR=1.07, P=0.000396) and proliferative DR (OR=1.67, P=3.699068E-14). All the findings were robust across several sensitivity analyses. Conclusion: Consistent with previous clinical studies, our findings revealed a positive correlation between DR and DN, providing genetic evidence for the non-invasive nature of DR in predicting DN.