Article Text

Download PDFPDF
Genetic associations of myopia severities and endophenotypes in children
  1. Fen Fen Li1,
  2. Shi Yao Lu1,
  3. Shu Min Tang1,2,
  4. Ka Wai Kam1,3,
  5. Tam Pancy O S1,
  6. Wilson W K Yip1,3,
  7. Alvin L Young1,3,
  8. Clement C Tham1,4,
  9. Chi Pui Pang1,
  10. Jason C. Yam1,
  11. Li Jia Chen1,3
  1. 1 Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China
  2. 2 Department of Ophthalmology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
  3. 3 Department of Ophthalmology and Visual Sciences, Prince of Wales Hospital, Hong Kong, China
  4. 4 Hong Kong Eye Hospital, Hong Kong, China
  1. Correspondence to: Dr Jason C. Yam and Dr Li Jia Chen, Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong Eye Hospital, 147K Argyle Street, Kowloon, Hong Kong, China; email: and lijia_chen{at}


Objective To investigate the associations of multiple single-nucleotide polymorphisms (SNPs) with the severities and endophenotypes of myopia in children.

Methods A total of 3300 children aged 5–10 years were recruited: 137 moderate and high myopia (SE≤−3.0D), 670 mild myopia (−3.0D<SE≤−0.5D) and 2493 controls (SE>−0.5D). 13 SNPs in 13 genes/loci were selected for genotyping in all subjects using TaqMan assays. Associations between each SNP with myopia severities and ocular traits (spherical equivalent (SE), axial length (AL) and corneal radius (CR)) were analysed.

Results When compared with controls, SNPs ZC3H11B rs4373767 (OR=1.15, p=0.038), BICC1 rs7084402 (OR=1.18, p=0.005) and GJD2 rs524952 (OR=1.14, p=0.025) showed nominal associations with overall myopia. ZC3H11B rs4373767 and BICC1 rs7084402 showed stronger associations with moderate and high myopia (rs4373767: OR=1.42, p=0.018; rs7084402: OR=1.33, p=0.025), while GJD2 rs524952 had a stronger association with mild myopia (OR=1.14, p=0.025). GJD2 rs524952 also showed a difference between emmetropia and hyperopia (p=0.018). In quantitative trait locus analysis, ZC3H11B rs4373767, KCNQ5 rs7744813 and GJD2 rs524952 were correlated with both myopic SE (β=−0.09, p=0.03; β=−0.12, p=0.007; β=−0.13, p=0.0006, respectively) and AL (β=0.07, p=0.002; β=0.09, p=0.0008; β=0.07, p=0.0003, respectively). SNTB1 rs7839488 was correlated with both AL (β=0.07, p=0.005) and CR (β=0.02, p=0.006). Moreover, ZC3H11B rs4373767-T (β=0.006; p=0.018), KCNQ5 rs7744813-A (β=0.007; p=0.015) and GJD2 rs524952-T (β=0.009; p=0.0006) were correlated with AL-CR ratio.

Conclusions and Relevance ZC3H11B and BICC1 are genetic risk factors for moderate and high myopia, while ZC3H11B, KCNQ5, SNTB1 and GJD2 confer risk to excessive AL in children.

  • Genetics
  • Child health (paediatrics)
  • Optics and Refraction

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.


  • Contributors LJC, JCY and CPP conceived the idea and designed the study. LJC, JCY, KWK and WWKY recruited the study subjects and performed clinical examinations., FFL, SYL, SMT and POST performed the experiments. FFL analysed the data and wrote the manuscript. LJC, JCY, CPP, CCT and ALY revised the paper. All authors approved the submitted version.

  • 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 (JCY)); 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 (JCY). 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.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.

Linked Articles

  • At a glance
    Frank Larkin