Article Text

Download PDFPDF
Association of polymorphisms in ZFHX1B, KCNQ5 and GJD2 with myopia progression and polygenic risk prediction in children
  1. Li Jia Chen1,2,3,
  2. Fen Fen Li1,4,
  3. Shi Yao Lu1,
  4. Xiu Juan Zhang1,
  5. Ka Wai Kam1,2,
  6. Shu Min Tang1,5,
  7. Pancy OS Tam1,
  8. Wilson WK Yip1,2,
  9. Alvin L Young1,2,
  10. Clement C Tham1,2,3,6,
  11. Chi Pui Pang1,2,3,
  12. Jason C Yam1,2,3,6
  1. 1 Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China
  2. 2 Department of Ophthalmology and Visual Sciences, Prince of Wales Hospital, Hong Kong, China
  3. 3 Hong Kong Hub of Paediatric Excellence, The Chinese University of Hong Kong, Hong Kong, China
  4. 4 Department of Ophthalmology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
  5. 5 Department of Ophthalmology, First Affiliated Hospital of Fujian Medical University, Xiamen, China
  6. 6 Hong Kong Eye Hospital, Hong Kong, China
  1. Correspondence to Dr Li Jia Chen, Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong; lijia_chen{at}; Dr Jason C Yam; yamcheuksing{at}


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.

  • genetics
  • optics and refraction

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information. N/A.

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information. N/A.

View Full Text


  • 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.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

Linked Articles

  • At a glance
    Frank Larkin