Genetic associations of myopia severities and endophenotypes in children

ObjectiveTo investigate the associations of multiple single-nucleotide polymorphisms (SNPs) with the severities and endophenotypes of myopia in children.MethodsA 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.ResultsWhen compared with controls, SNPs ZC3H11Brs4373767 (OR=1.15, p=0.038), BICC1rs7084402 (OR=1.18, p=0.005) and GJD2rs524952 (OR=1.14, p=0.025) showed nominal associations with overall myopia. ZC3H11Brs4373767 and BICC1rs7084402 showed stronger associations with moderate and high myopia (rs4373767: OR=1.42, p=0.018; rs7084402: OR=1.33, p=0.025), while GJD2rs524952 had a stronger association with mild myopia (OR=1.14, p=0.025). GJD2rs524952 also showed a difference between emmetropia and hyperopia (p=0.018). In quantitative trait locus analysis, ZC3H11Brs4373767, KCNQ5rs7744813 and GJD2rs524952 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). SNTB1rs7839488 was correlated with both AL (β=0.07, p=0.005) and CR (β=0.02, p=0.006). Moreover, ZC3H11Brs4373767-T (β=0.006; p=0.018), KCNQ5rs7744813-A (β=0.007; p=0.015) and GJD2rs524952-T (β=0.009; p=0.0006) were correlated with AL-CR ratio.Conclusions and RelevanceZC3H11Band BICC1are genetic risk factors for moderate and high myopia, while ZC3H11B, KCNQ5, SNTB1and GJD2confer risk to excessive AL in children.