Abstract:[Abstract] Objective This study aimed to evaluate whether Wnt pathway-related genes previously implicated in high myopia (HM) could serve as candidate genes for HM in the Chinese Han population and to identify risk loci associated with HM susceptibility. Mthods A case-control association analysis was conducted involving 530 HM patients and 1087 healthy controls. The test efficacy was estimated using Quanto software. Peripheral blood DNA was extracted using the magnetic bead method, and seven candidate single nucleotide polymorphisms (SNPs) were genotyped using the Sequenom MassARRAY system. The SNPs analyzed were HIVEP3 rs17365632, rs35134694, rs11210537; TNNB1 rs13072632; CAMK2NA rs10753502; Wnt7B rs73175083; and TCF4 rs41396445. Differences in allele and genotype frequencies between the HM and control groups were compared using the chi-square test under dominant, recessive, and additive inheritance models. Haplotype analysis was performed using SHEsis online software. Statistical significance was set at Pc < 0.05 after Bonferroni correction. Results All seven SNPs had a genotyping detection rate exceeding 90% and were in Hardy-Weinberg equilibrium (P > 0.05). The test efficacy of the sample size was above 90.13%, indicating that the samples were representative of the population. In the HM group, the AA genotype frequency of HIVEP3 rs11210537 was significantly reduced (Pc = 0.003,OR = 0.889). Conversely, the GG genotype frequency was significantly elevated (Pc = 0.003,OR = 1.176). In an additive genetic model (AA vs GG), the AA genotype frequency was significantly lower than the GG genotype frequency (Pc = 0.003, OR = 0.583). Additionally, the frequency of the CCA haplotype of rs17365632, rs35134694, and rs11210537 in HIVEP3 was decreased in the HM group compared to the control group (Pc = 0.008, OR = 0.791). Conclusions The SNP locus rs11210537 in the HIVEP3 gene is associated with genetic susceptibility to HM in the Chinese Han population, with the G allele and GG genotype identified as risk genetic markers. The CCA haplotype of rs17365632, rs35134694, and rs11210537 in the HIVEP3 gene represents a risk haplotype for HM.