Genetic associations of myopia severities and endophenotypes in children.

Abstract

To investigate the associations of multiple single-nucleotide polymorphisms (SNPs) with the severities and endophenotypes of myopia in children. A total of 3300 children aged 5-10 years were recruited: 137 moderate and high myopia (SE≤-3.0D), 670 mild myopia (-3.0D<SE≤-0.5D) and 2493 controls (SE>-0.5D). 13 SNPs in 13 genes/loci were selected for genotyping in all subjects using TaqMan assays. Associations between each SNP with myopia severities and ocular traits (spherical equivalent (SE), axial length (AL) and corneal radius (CR)) were analysed. When compared with controls, SNPs <i>ZC3H11B</i> rs4373767 (OR=1.15, p=0.038), <i>BICC1</i> rs7084402 (OR=1.18, p=0.005) and <i>GJD2</i> rs524952 (OR=1.14, p=0.025) showed nominal associations with overall myopia. <i>ZC3H11B</i> rs4373767 and <i>BICC1</i> rs7084402 showed stronger associations with moderate and high myopia (rs4373767: OR=1.42, p=0.018; rs7084402: OR=1.33, p=0.025), while <i>GJD2</i> rs524952 had a stronger association with mild myopia (OR=1.14, p=0.025). <i>GJD2</i> rs524952 also showed a difference between emmetropia and hyperopia (p=0.018). In quantitative trait locus analysis, <i>ZC3H11B</i> rs4373767, <i>KCNQ5</i> rs7744813 and <i>GJD2</i> rs524952 were correlated with both myopic SE (β=-0.09, p=0.03; β=-0.12, p=0.007; β=-0.13, p=0.0006, respectively) and AL (β=0.07, p=0.002; β=0.09, p=0.0008; β=0.07, p=0.0003, respectively). <i>SNTB1</i> rs7839488 was correlated with both AL (β=0.07, p=0.005) and CR (β=0.02, p=0.006). Moreover, <i>ZC3H11B</i> rs4373767-T (β=0.006; p=0.018), <i>KCNQ5</i> rs7744813-A (β=0.007; p=0.015) and <i>GJD2</i> rs524952-T (β=0.009; p=0.0006) were correlated with AL-CR ratio. <i>ZC3H11B</i> and <i>BICC1</i> are genetic risk factors for moderate and high myopia, while <i>ZC3H11B, KCNQ5, SNTB1</i> and <i>GJD2</i> confer risk to excessive AL in children.