ObjectiveTo investigate the relationship between single nucleotide polymorphisms (SNP) in the CHRM1 gene and genetic susceptibility to high myopia (HM) in the Han population of Henan Province. MethodsA retrospective case-control study. From January 2021 to April 2023, 576 HM patients (HM group) and 768 healthy volunteers (control group) were recruited from the Department of Ophthalmology, the First Affiliated Hospital of Zhengzhou University. All participants were of Han ethnicity from Henan Province. SNP data for the CHRM1 gene in the Northern Han Chinese population were downloaded from the 1000 Genomes Project Online Website, with screening criteria of Hardy-Weinberg equilibrium P＞0.05 and minor allele frequency＞0.05. Haploview software was used to analyze HapMap genotypes, identifying 5 tagSNP: rs55885673, rs544978, rs56995061, rs1942499, and rs2075748. MassARRAY system was employed for genotyping the 5 tagSNP loci. The SHEsis online software was employed to analyze the distribution differences of genotypes and allele frequencies between the two groups. Linkage disequilibrium coefficient D' was used to evaluate the recombination events between SNP loci, and haplotypes with frequencies exceeding 3% were constructed for statistical analysis. Results The age of the HM group was significantly lower than that of the control group (t=18.515, P＜0.05), while no significant difference was observed in gender distribution (χ2=2.869, P=0.087). Compared with the control group, the HM group showed significantly higher frequencies of the C allele [odds ratio (OR)=1.44, 95% confidence interval (CI): 1.09-1.91, Pc=0.045)] and CC genotype (OR=1.50, 95% CI: 1.11-2.02, Pc=0.038) at the rs56995061 locus, and significantly lower frequencies of the T allele (OR=0.69, 95%CI: 0.52-0.91, Pc=0.045) and CT genotype (OR=0.67, 95%CI: 0.49-0.91, Pc=0.045). Additionally, the CT genotype frequency at the rs2075748 locus was significantly lower in the HM group (OR=0.66, 95%CI: 0.53-0.84, Pc=0.002). The haplotype G-T-A-A formed by rs55885673-rs56995061-rs1942499-rs544978 was significantly less frequent in the HM group (OR=0.71, 95%CI: 0.54-0.94, P=0.170). ConclusionsThe polymorphisms at the SNP loci rs56995061 and rs2075748 in the CHRM1 gene are associated with the genetic susceptibility to high myopia in the Chinese Han population. The G-T-A-A haplotype composed of rs55885673-rs56995061-rs1942499-rs544978 reduces the susceptibility to high myopia.