Purpose Five genome-wide association studies (GWAS) of myopia identified that single nucleotide polymorphisms (SNPs) in 4q25, 11q24, CTNND2, 15q14 and 15q25 were associated with myopia. We are aimed to replicate these significant associations with high myopia in Chinese population.
Method 8 most significant SNPs in previous GWAS study were selected, including rs10034228 in 4q25, rs12716080, rs6885224 in CTNND2, rs577948 in 11q24, rs634990, rs524952 in 15q14, rs8027411 and rs939658 in 15q25. These SNPs were genotyped by restriction fragment length polymorphisms or by unlabelled probe melting analysis in 751controls (-1.00D2test and logistic regression model in Plink. Linkage disequilibrium (LD) patterns were constructed by Haploview. Association studies of haplotype were performed by Plink.
Result All the genotypes were in HWE (P>0.05) for all SNPs in the controls. By single-marker analysis we identified significant association with high myopia only for two SNPs, rs524952 (p=2.69E-08) and rs634990 (p=3.65E-08) in 15q14. For the two SNPs, we found one protective haplotype--TT (OR=0.67, P=9.03*10-8) and one high-risk haplotype--AC (OR=1.53, P=1.02*10-8). Haplotypes constructed by rs939658 and rs8027411 in 15q25 also associated with high myopia. The protective haplotype is AG (OR=0.83, P= 0.0099) and the high-risk haplotype is AT (OR=2.69, P= 0.0087). The results remained significant after multiple comparison correction by 50000 permutations. No other SNPs were statistically associated with high myopia.
Conclusion We confirmed the associations between SNPs in 15q14 and 15q25 with high myopia in Hong Kong Chinese cohorts, and can not successfully replicate other GWAS studies.