Genetic Association Study Between Refractive Error-Related Genes and High Myopia in the Chinese Han Population

Refractive errors are the leading cause of visual impairment and blindness globally. High myopia (HM) poses significant risks of severe ocular complications and blindness. 12 SNPs, including rs580839, have been associated with refractive errors in European and Asian populations, but their roles in Chinese cohorts remain unexplored. Their genetic association with HM is investigated in this study.

Genotyping of specific SNPs was conducted using multiplexed SNP/exome capture sequencing in a cohort consisting of HM patients and emmetropic individuals. The 3DSNP and GTEx databases were used to identify the causal association between SNPs and regulated genes. In addition, a mouse form-deprivation myopia (FDM) model was established, and retinal protein levels were quantified by the western blot analysis.

Our study revealed that the heterozygous genotype of GJD2-rs580839 (G/A) was associated with HM in both the heterozygous (GA vs. GG: p = 0.021, OR = 1.433) and dominant (GA + AA vs. GG: p = 0.026, OR = 1.388) inheritance models. GTEx database indicates that the aforementioned risk genotypes (rs580839-AG and rs580839-AG + AA) are associated with the regulation of GJD2 gene expression. In the FDM mouse model, a significant downregulation of C × 36 protein expression was observed.

This study showed a statistically suggestive association between rs580839 (GJD2) and HM among the Han Chinese population. In addition, rs580839 may influence the pathogenesis of HM through the C × 36-mediated pathway. However, further in vivo studies are required to elucidate the complex mechanisms that underlie HM development.