Causal Effects of Dietary Macronutrients and Micronutrients on Myopia and Other Major Ocular Disorders: A Mendelian Randomization Study

Summary

This protocol describes a method for investigating the causal effects of dietary nutrients on ocular diseases using Mendelian randomization analysis. This approach enables the identification of potential nutritional risk and protective factors for major eye disorders.

Abstract

Myopia and other major ocular disorders, such as cataracts, glaucoma, and age-related macular degeneration (AMD), pose growing public health concerns worldwide. While nutrition is believed to influence ocular development and degeneration, causal evidence remains limited. A two-sample Mendelian randomization (MR) analysis was performed using large-scale genome-wide association study (GWAS) summary data to evaluate the causal effects of dietary macronutrient and micronutrient intake on the risk of myopia and other ocular diseases. The inverse variance-weighted (IVW) method was used as the primary analysis, supported by weighted median, MR-Egger, and MR-PRESSO for sensitivity testing. To account for multiple comparisons, false discovery rate (FDR) correction was applied. After FDR adjustment, higher genetically predicted vitamin C levels remained significantly associated with an increased risk of AMD (odds ratio [OR] = 1.324, 95% confidence interval [CI]: 1.133–1.546). Several additional associations were observed at nominal significance levels (P < 0.05), including higher relative dietary fat intake with increased myopia risk (OR = 1.033, 95% CI: 1.003–1.063), sugar intake with reduced cataract risk (OR = 0.746, 95% CI: 0.561–0.993), iron with lower myopia risk (OR = 0.995, 95% CI: 0.991–0.999), vitamin D with increased cataract risk (OR = 1.256, 95% CI: 1.062–1.487), folic acid with reduced cataract risk (OR = 0.843, 95% CI: 0.724–0.981), and phosphorus with reduced glaucoma risk (OR = 0.727, 95% CI: 0.554–0.953). No evidence of horizontal pleiotropy or heterogeneity was observed. These findings suggest a potential causal role of certain nutrients in ocular disease risk, although most associations did not remain significant after multiple testing correction and should therefore be interpreted with caution. Further studies are needed to confirm these findings and explore underlying biological mechanisms.

Introduction

Visual impairment caused by ocular disorders represents a growing global public health challenge, with significant socioeconomic and quality-of-life implications^1,2,3. Among these conditions, refractive error has emerged as a leading cause of vision loss, especially in East and Southeast Asia, where its prevalence among young adults reaches 80–90%, and high myopia affects up to 20% of the population⁴. More recent epidemiological evidence suggests that myopia prevalence continues to increase globally, and newer studies have highlighted the contrib....

Protocol

The Mendelian Randomization (MR) analyses utilized data from a publicly accessible GWAS (https://gwas.mrcieu.ac.uk/), which had already obtained the necessary ethical and informed consent approvals during the initial data collection. Consequently, no further ethical or informed consent was required for the study. The software and the databases used are listed in the Table of Materials.

1. Exposure data

GWAS summary information on relative dietary macronutrient intake of fat, protein, carbohydrates, and sugar was obtained from over 235,000 individuals of European ancestries

Results

The significant causal effects of dietary macronutrient and micronutrient intake on myopia and other major ocular disorders, as identified by the IVW method, are summarized in Table 3 and presented in Figure 2. To account for multiple comparisons across multiple exposures and outcomes, FDR correction was applied. After FDR adjustment, only the association between genetically predicted vitamin C levels and increased risk of early AMD remained statistically significant (OR = 1.......

Discussion

In this study, the potential causal effects of dietary macronutrient and micronutrient intake on the risk of myopia and other major ocular disorders, including cataracts, glaucoma, and AMD, were systematically evaluated. After correcting for multiple comparisons using the false discovery rate (FDR) method, only the association between genetically predicted vitamin C levels and increased risk of AMD remained statistically significant. Several additional associations were observed at nominal significance levels, including .......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
IEU GWAS database	MRC Integrative Epidemiology Unit, University of Bristol	www.gwas.mrcieu.ac.uk	Source of GWAS summary statistics
MR-PRESSO R package	GitHub (MR-PRESSO developers)	www.github.com/rondolab/MR-PRESSO	Used for detecting pleiotropy and outliers
R software (version 4.1.2)	The R Foundation	www.r-project.org	Used for all statistical analyses and Mendelian randomization
TwoSampleMR R package	MRC Integrative Epidemiology Unit	www.mrcieu.github.io/TwoSampleMR	Used for Mendelian randomization analysis