Causality of Diabetic Nephropathy and Age-Related Macular Degeneration: A Mendelian Randomization Study

Age-related macular degeneration (AMD) currently stands as the leading cause of irreversible vision loss in the present era. The primary objective of this study was to investigate the causal relationships between diabetic nephropathy (DN), its associated risk factors, and AMD among participants of European descent.

Genetic variants associated with DN and its risk factors, encompassing glycemic traits, lipidemic traits, systolic/diastolic blood pressure, obesity, and urate, were obtained from previously published genome-wide association studies. Summary-level statistics for AMD were acquired from the FinnGen database. Univariable and multivariable Mendelian randomization (MR) were employed to conduct this investigation.

Our MR analyses indicated that per 1-standard deviation (SD) increase of DN heightened the risk of overall AMD (p = 1.03 × 10^-8, OR = 1.24). And these findings remained consistent when examining both dry AMD (p = 2.27 × 10^-4, OR = 1.17) and wet AMD (p = 5.15 × 10^-6, OR = 1.33). Additionally, there was a causal association between high-density lipoprotein-cholesterol (HDL-C) levels and an increased risk of AMD (p = 2.69 × 10^-3, OR = 1.23), while triglycerides were found to mitigate the risk (p = 0.02, OR = 0.83). Notably, no significant associations were observed between other risk factors of DN and AMD.

These findings suggest that the impact of DN on the development of AMD may be more substantial than previously believed. Furthermore, elevated HDL-C levels appear to heighten the risk of AMD, whereas triglycerides may provide a protective effect.