AimsHigh myopia is a common visual disorder in the world. The ZNF644, GRM6, and CTNND2 genes are expressed in the retina. This study aims to investigate the associations of these genes with high myopia in Han Chinese population.MethodsThe case-control association included high myopia cases (n=430) and controls (n=430) recruited from a population-based study, 'Jiangsu Eye Study'. Fourteen single-nucleotide polymorphisms (SNPs) in three genes were genotyped by the TaqMan method using the real-time PCR system.ResultsThree SNPs GRM6-rs11746675, GRM6-rs2067011, and GRM6-rs2645339 were associated with high myopia (odds ratio (OR)=0.74, P=0.003; OR=0.78, P=0.018; and OR=0.78, P=0.023; respectively). The significances of rs2067011 and rs2645339 disappeared after multiple testing corrections. Rs11746675 remained significant after correction for multiple testing. The genetic model analysis found that GRM6-rs11746675 and GRM6-rs2067011 were suggestively associated with high myopia in the recessive model (OR=0.54, P=0.004; OR=0.52, P=0.003; respectively). Haplotype GAT for GRM6 markers rs2067011-rs2645339-rs762724 showed significance (P=0.0239), but such association did not remain significant after multiple testing corrections.ConclusionsOur data suggested that genetic variants in GRM6 are associated with high myopia. The mechanism of GRM6 in the development of high myopia need to be further investigated.