Aims To assess the association of single-nucleotide polymorphisms (SNPs) with myopia progression for polygenic risk prediction in children.
Methods Six SNPs (ZC3H11B rs4373767, ZFHX1B rs13382811, KCNQ5 rs7744813, MET rs2073560, SNTB1 rs7839488 and GJD2 rs524952) were analysed in 1043 school children, who completed 3-year follow-up, using TaqMan genotyping assays. SNP associations with progression in spherical equivalent (SE) were analysed by logistic regression. Polygenic risk scores (PRS) were applied for computing the sum of the risk alleles of multiple SNPs corresponding to myopia progression, weighted by the effect sizes of corresponding SNPs.
Results GJD2 rs524952 showed significant association with fast progression (OR=1.32, 95% CI 1.10 to 1.59; p=0.003) and KCNQ5 rs7744813 had nominal association (OR=1.32, 95% CI 1.04 to 1.67; p=0.02). In quantitative traits locus analysis, GJD2 rs524952 and KCNQ5 rs7744813 were associated with progression in SE (β=−0.038 D/year, p=0.008 and β=−0.042 D/year, p=0.02) and axial elongation (β=0.016 mm/year, p=0.01 and β=0.017 mm/year, p=0.027). ZFHX1B rs13382811 also showed nominal association with faster progression in SE (β=−0.041 D/year, p=0.02). PRS analysis showed that children with the highest PRS defined by rs13382811, rs7744813 and rs524952 had a 2.26-fold of increased risk of fast myopia progression (p=4.61×10−5). PRS was also significantly associated with SE progression (R2=1.6%, p=3.15×10−5) and axial elongation (R2=1.2%, p=2.6×10−4).
Conclusions In this study, multi-tiered evidence suggested SNPs in ZFHX1B, KCNQ5 and GJD2 as risk factors for myopia progression in children. Additional attention and appropriate interventions should be given for myopic children with high-risk PRS as defined by GJD2 rs524952, KCNQ5 rs7744813 and ZFHX1B rs13382811.
- optics and refraction
Data availability statement
All data relevant to the study are included in the article or uploaded as supplementary information. N/A.
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LJC and FFL are joint first authors.
Contributors LJC and JCY designed and supervised this study, and critically revised the manuscript. FFL and SYL conducted the experiments, collected and analyzed the data, and drafted the manuscript. LJC, JCY, XJZ, KWK, SMT, WWKY, ALY, and CCT recruited the study subjects. POST prepared the DNA samples and provided technical support. CPP provided logistic support and scientific comments. All authors approved the final draft of the manuscript.
Funding The work in this paper was supported in part by the research grants from the Health and Medical Research Fund Hong Kong (05160836 (LJC)); the General Research Fund, Hong Kong (14111515 and 14103419 (JCSY)); a Direct Grant from the Chinese University of Hong Kong (4054486 (LJC); the Endowment Fund for Lim Por-Yen Eye Genetics Research Centre, Hong Kong; the CUHK Jockey Club Children Eye Care Programme; and the Centaline Myopia Fund (JCSY).
Disclaimer The funding organisations had no roles in the design or conduct of this research. They also had no role in reviewing the manuscript or decision on submission of the manuscript.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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