Investigating causal associations of circulating micronutrient concentrations with the risk of age-related macular degeneration and diabetic retinopathy: A Mendelian randomization study

Abstract

Background: Age-related macular degeneration (AMD) and diabetic retinopathy (DR) are two prevalent retinal neovascular diseases globally. Although observational studies have suggested a link between micronutrients and both AMD and DR, the causal relationship remains unconfirmed.

Methods: The causal estimation was performed using the Mendelian randomization (MR) method. Single-nucleotide polymorphisms (SNPs) for circulating micronutrient levels were sourced from published genome-wide association studies (GWAS). Data for AMD and DR GWAS were obtained from the FinnGen consortium. The inverse variance weighted (IVW) method served as the primary MR analysis, with sensitivity analyses conducted to validate the MR hypothesis. Additionally, a reverse MR analysis was performed to assess the potential influence of reverse causality in our MR study.

Results: The MR analysis using the IVW method indicated that magnesium is associated with a reduced risk of AMD (OR: 0.687, 95% CI: 0.512-0.921, p = 0.012) and wet AMD (OR: 0.640, 95% CI: 0.433-0.944, p = 0.025). Furthermore, vitamin B6 is linked to a decreased risk of DR (OR: 0.754, 95% CI: 0.574-0.990, p = 0.042). The reverse MR analysis did not detect any reverse causality.

Conclusions: This study found that genetically determined serum magnesium is associated with a reduced risk of AMD, and genetically determined serum vitamin B6 is associated with a decreased risk of DR. These findings suggest that magnesium and vitamin B6 could be potential therapeutic targets for both AMD and DR, respectively.

Keywords

age-related macular degeneration / circulating micronutrients / diabetic retinopathy / magnesium / Mendelian randomization / vitamin B6

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