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

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.