The roles of PAX6 and SOX2 in myopia: Lessons from the 1958 British Birth Cohort

Abstract

PURPOSE. Myopia is a common complex trait that affects up to 60% of some populations. Its development is influenced by multiple genes and environmental factors. PAX6 and SOX2 are genes with fundamental roles in ocular growth and development, and they have been linked with myopia in a recent linkage study. The authors investigated the roles of PAX6 and SOX2 in common myopia as part of a broader association study of refractive error. METHODS. Five hundred ninety-six persons from the 1958 British Birth Cohort, a nationally representative population, were randomly selected from the outer tertiles of the refractive error (RE) distribution and were genotyped using 25 tagSNPs across PAX6 and 3 tagSNPs across SOX2 and their putative control regions. This experiment had 80% power to exclude either gene contributing more than 10% of the variance of refractive error. RESULTS. All SNPs were in Hardy-Weinberg equilibrium, and the genotyping failure rate was less than 5%. Accounting for multiple testing, no significant association (P < 0.05) was found between any of the SNPs or haplotypes and refractive error. CONCLUSIONS. PAX6 and SOX2 are obvious candidates in RE genetic studies because of their biological roles and prior linkage studies. The present findings strongly suggest refractive error is not directly affected in this population by variants in either gene or by their known promoters/enhancers. The authors suggest that neither PAX6 nor SOX2 should be prioritized in the international search for genetic modifiers of refractive error. Their findings contribute to broader understanding of the pathophysiology of refractive error and highlight the critical role of replication in genetic research on complex disorders. Copyright © Association for Research in Vision and Ophthalmology.