Associations Between Myopia and Brain Volumes: An Observational and Genetic Analysis

Abstract

Purpose: To examine phenotypic and genetic associations between myopia and various brain volumes using the UK Biobank database.

Methods: After 1:1 propensity score matching (PSM) between participants with myopia and healthy controls, the relationship between myopia and brain volumes was examined using general linear regression, with adjustments for covariates including age, sex, ethnicity, Townsend Deprivation Index, lifestyle factors, and disease status. Bonferroni correction was applied for multiple comparisons. Bidirectional Mendelian randomization (MR) and genetic risk score (GRS) were used to assess genetic associations.

Results: After Bonferroni correction, general linear regression revealed that myopia was significantly associated with reduced total brain volume (β, -0.07 mL; 95% confidence interval [CI], -0.11 to -0.03) and white matter volume (β, -0.08 mL; 95% CI, -0.13 to -0.03) in the fully adjusted model. Education significantly modified the myopia-gray matter association, with a stronger negative correlation in individuals without a college education (β, -0.09 mL; 95% CI, -0.15 to -0.04). MR analysis indicated no obvious causal effect of myopia on brain volumes, and GRS analysis revealed only a slight decreasing trend in total brain volume with increasing genetic risk for myopia (P value for trend < 0.05).

Conclusions: Although myopia shows phenotypic associations with brain volumes, including total brain and white matter, and particularly with gray matter in individuals with lower education, genetic analysis (MR and GRS) did not support a causal or genetic link with brain volumes. These findings suggest that residual confounding factors beyond education level may underlie the observed associations between myopia and brain volumes, underscoring the need for further research to elucidate these relationships.

Figure 1.

The study explored both phenotypic and genetic associations between myopia and various brain volumes. The phenotypic relationship between myopia and brain volumes was examined using general linear regression and subgroup analysis. The genetic analysis was conducted by bidirectional Mendelian randomization and genetic risk score. The sensitivity analysis was performed in the white population without missing values.

Figure 2.

Flowchart depicting population selection from the UK Biobank in this study.

Figure 3.

Subgroup analysis for the correlation between myopia and gray matter volume. General linear regression models were employed to assess the interaction effects of myopia with age, sex, and education on gray matter volume. Model 1 was adjusted for age, sex, ethnicity, and Townsend Deprivation Index; model 2 was adjusted for model 1 plus alcohol consumption, smoking status, at or above moderate/vigorous/walking recommendations, body mass index, and years of education; model 3 was adjusted for model 2 plus hyperlipidemia, diabetes, and hypertension. Horizontal lines represent the ranges of the 95% CIs, and the vertical dashed lines represent the mean of 0.0.