PAX6 and SOX2 Are Not Associated With Myopia: Findings From the 1958 British Birth Cohort

Abstract

Purpose:: PAX6 and SOX2 are known to play a critical role in ocular development, making them good candidates for refractive error. We investigated the role of PAX6 and SOX2 in physiological (primary non-syndromic) myopia, as part of a broader association study of refractive error.

Methods:: Subjects were drawn from 2494 people randomly selected from the 1958 British Birth Cohort (comprising everyone born in Great Britain in one week in March 1958), who had autorefraction undertaken at age 44. The mean spherical equivalent of refraction of both eyes was calculated for each individual. 248 individuals were selected at random from each of the outer tertiles of the distribution. Tagging single nucleotide polymorphisms (SNPs) were chosen using the Tagger algorithm and genotyped on the Illumina GoldenGate platform. Analysis was performed using the qualitative trait (myopic vs. non-myopic) as well as the mean spherical equivalent as a quantitative trait. Individual SNP analysis was undertaken using regression in Stata. Single SNP and haplotype analyses performed using the likelihood ratio test in Whap. In total for the overall study,1536 tag SNPs were chosen across 111 genes. Of these, 25 SNPs were chosen to span a 404 Kb region that included PAX6 and putative control regions. 3 SNPs were selected across a 10.8 Kb region that centred on SOX2 and included putative control regions. Given the sample size, this experiment has 80% power to exclude either gene contributing to more than 10% of the variance of the refractive error in this cohort.

Results:: All SNPs in PAX6 and SOX2 were in Hardy Weinberg equilibrium and the genotyping failure rate was < 5%. After accounting for multiple testing, no statistically significant association (p < 0.05) could be found between any of the SNPs or haplotypes and refractive error.

Conclusions:: We suggest that PAX6 and SOX2 are unlikely to be significant modifiers of refraction. Other candidate genes and regions should therefore be prioritized in further research into refractive error.

Keywords: myopia • genetics • refractive error development