Rs10034228

rs10034228 is a SNP that has been associated with pathological myopia (nearsightedness) in Han Chinese. Pathological myopia refers to an error in refractive index greater than -6.0 diopters (D), and it may be associated with degeneration in the back of the eye. This SNP is a C/T variant in an intergenic region of chromosome 4q25. The ancestral allele is T. Two reports to date have identified the significance of this association.

The first report conducted a GWAS in three stages on a total of 2,993 cases and 10,406 controls from Zhejiang Province and Shanghai, both in China. The first stage examined older patients with severe myopia (mean refraction < -8.00 D) suffering from retinal degeneration, the second stage examined adolescents with milder myopia (mean refraction = -6.70 D ± 1.61), and the third stage examined a broader population (mean refraction = -12.21 D ± 4.89). Meta-analysis of these results identified that rs10034228(T) is protective from myopia (p = 7.70 x 10-8, OR = 0.81, 95% confidence interval 0.76–0.86), and that rs10034228(C) is associated with myopia. They also observed that the SNP is within the MYP11 locus, a locus for autosomal dominant high myopia identified in a Chinese family [PMID: 16052171]. There are no known genes in the region, although there are expressed sequence tags, a predicted gene, and enhancers. Nominal associations for rs2218817 (p = 4.16 × 10-25), rs4440293 (p = 5.49 × 10-25), rs1585471 (p = 2.14 × 10-26), and rs6837348 (p = 3.21 × 10-26) were also discovered.

Interestingly, SNPs significantly associated with myopia identified in previous GWA studies in different populations (rs577948 in Japanese samples, rs634990 in Caucasian samples , and rs8027411 ) were not significant in this first report, a finding that the authors attributed to genetic heterogeneity between ethnicities, differences in clinical criteria for myopic cases, and complexity of the trait.

The results of the first report were subsequently validated in a case-control study of university students in Guangzhou, China. In this study, there were 1052 controls (mean refraction = -0.5 D to +2.00 D), 615 moderate myopia cases (-4.00 D to -6.00 D), and 640 high myopia cases (mean refraction = ≤ -6.00 D). Notably, these cases of myopia were less severe than in the aforementioned GWAS. The study validated five SNPs in 4q25 associated with high myopia in Chinese adults from the previous study: rs2218817 (p = 0.009, OR = 1.18), rs1585471 (p = 0.007, OR = 1.19), rs6837348 (p = 0.012, OR = 1.18), and rs10034228 (p = 0.009, OR = 1.18). There was no significant difference found between the moderate myopia group and high myopia group.

A GWAS meta-analysis of 2793 cases and 4643 controls from various cities in China, also investigating myopia, found three additional SNPs associated with myopia (rs2597881, rs326896 and rs12508492) and found that the these SNPs are in the same LD block of the HapMap HCB (Han Chinese in Beijing) database as rs10034228 and other myopia-associated SNPs. This finding further corroborates the association of rs10034228 with myopia. Notably, in this study, the patients had more severe myopia (mean refractive index OD (right eye) = -11.21 D ± 3.92, mean refractive index OS (left eye) = 10.74 D ± 3.65).}}

Nearsightedness and Farsightedness


 * is_associated_with_disease::Retinal degeneration
 * is_associated_with_disease::Degenerative myopia