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Laboratory science
Association of SIX1-SIX6 polymorphisms with peripapillary retinal nerve fibre layer thickness in children
  1. Shi Yao Lu1,
  2. Xiu Juan Zhang1,
  3. Yu Meng Wang1,
  4. Nan Yuan1,
  5. Ka Wai Kam1,2,
  6. Poemen P Chan1,3,
  7. Pancy OS Tam1,
  8. Wilson WK Yip1,2,
  9. Alvin L Young1,2,
  10. Clement C Tham1,3,4,
  11. Chi Pui Pang1,4,
  12. Jason C Yam1,3,4,
  13. Li Jia Chen1,2,4
  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 Eye Hospital, Hong Kong, China
  4. 4 Hong Kong Hub of Paediatric Excellence, The Chinese University of Hong Kong, Hong Kong, China
  1. Correspondence to Dr Jason C Yam; yamcheuksing{at}cuhk.edu.hk; Dr Li Jia Chen, Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China; lijia_chen{at}cuhk.edu.hk

Abstract

Purpose Association of SIX1-SIX6 variants with peripapillary retinal nerve fibre layer (p-RNFL) thickness had been reported in adults. This study aimed to investigate these associations in children, with further explorations by spatial, age and sex stratifications.

Methods 2878 school children aged between 6 and 9 years were enrolled from the Hong Kong Children Eye Study. Three single-nucleotide polymorphisms (SNPs) at the SIX1-SIX6 locus were genotyped. The association of each SNP with p-RNFL thickness (including global and sectoral thickness) were evaluated using multiple linear regression.

Results SNPs rs33912345 (p=7.7×10−4) and rs10483727 (p=0.0013) showed significant associations with temporal-inferior p-RNFL thickness. The C allele of rs33912345 was associated with a thinner temporal-inferior p-RNFL by an average of 2.44 µm, while rs10483727-T was associated with a thinner temporal-inferior p-RNFL by 2.32 µm. The association with temporal-inferior p-RNFL was the strongest in the 8–9 year-old group for rs33912345 (p=5.2×10−4) and rs10483727 (p=3.3×10−4). Both SNPs were significantly associated with temporal-inferior p-RNFL thickness in boys (p<0.0017), but not in girls (p>0.05). In contrast, rs12436579-C (β=1.66; p=0.0059), but not rs33912345-C (β=1.31; p=0.052) or rs10483727-T (β=1.19; p=0.078), was nominally associated with a thicker nasal-inferior p-RNFL.

Conclusions Both rs33912345 and rs10483727 at SIX1-SIX6 were associated with p-RNFL thickness in children, especially at the temporal-inferior sector, with age-dependent and sex-specific effects. SNP rs12436579 was associated with nasal-inferior p-RNFL thickness. Our findings suggested a role of SIX1-SIX6 in RNFL variation during neural retina development in childhood.

  • genetics
  • glaucoma
  • child health (paediatrics)
  • imaging
  • optic nerve

Data availability statement

All data relevant to the study are included in the article or uploaded as online supplemental information. Not applicable.

https://doi.org/10.1136/bjophthalmol-2021-319756

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    Data availability statement

    All data relevant to the study are included in the article or uploaded as online supplemental information. Not applicable.

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    Footnotes

    • JCY and LJC are joint senior authors.

    • Contributors LJC is the guarantor responsible for the overall content of this article. LJC and SYL designed the study. JCY provided samples and management. CCT and CPP served as scientific advisors. KWK, PPC, WWY and ALY recruited the study subjects and collected data. POST was in charge of the sample storage and sample coding. SYL and NY conducted genetic experiments. XJZ and YMN managed the databases and provided statistical support. SYL and LJC drafted the manuscript, while other authors revised and approved the final version 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 and 07180256 (LJC)); the General Research Fund, Hong Kong (14111515 and 14 103 419 (JCY); 2141022 and 14105916 (CPP)); 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).

    • 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.

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