July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Association of Glaucoma Risk Variants with Retinal Nerve Fiber Layer Thickness: The Singapore Epidemiology of Eye Diseases (SEED) Study
Author Affiliations & Notes
  • Kok Yao Low
    Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore, Singapore
    Singapore Eye Research Institute , Singapore, Singapore
  • Yih Chung Tham
    Singapore Eye Research Institute , Singapore, Singapore
    Singapore National Eye Centre , Singapore , Singapore
  • Wanting Zhao
    Centre for Quantitative Medicine, Duke-NUS Medical School, Singapore, Singapore
    Singapore Eye Research Institute , Singapore, Singapore
  • Liang Zhang
    Singapore Eye Research Institute , Singapore, Singapore
  • Nicholas Tan
    Singapore Eye Research Institute , Singapore, Singapore
  • Charlene Wong
    Singapore Eye Research Institute , Singapore, Singapore
    Department of Ophthalmology, National University Hospital, Singapore, Singapore
  • Chiea Chuen Khor
    Genome Institute of Singapore, Agency for Science, Technology and Research, , Singapore, Singapore
  • Tin Aung
    Singapore Eye Research Institute , Singapore, Singapore
    Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore, Singapore
  • Tien Yin Wong
    Singapore Eye Research Institute , Singapore, Singapore
    Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore, Singapore
  • Ching-Yu Cheng
    Singapore Eye Research Institute , Singapore, Singapore
    Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore, Singapore
  • Footnotes
    Commercial Relationships   Kok Yao Low, None; Yih Chung Tham, None; Wanting Zhao, None; Liang Zhang, None; Nicholas Tan, None; Charlene Wong, None; Chiea Chuen Khor, None; Tin Aung, None; Tien Yin Wong, None; Ching-Yu Cheng, None
  • Footnotes
    Support  FY2017 AM-ETHOS Duke-NUS Medical Student Fellowship Orientation, NMRC/1249/2010, NMRC/CIRG/1371/2013, A*STAR BMRC 08/1/35/19/550
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 1813. doi:
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    • Get Citation

      Kok Yao Low, Yih Chung Tham, Wanting Zhao, Liang Zhang, Nicholas Tan, Charlene Wong, Chiea Chuen Khor, Tin Aung, Tien Yin Wong, Ching-Yu Cheng; Association of Glaucoma Risk Variants with Retinal Nerve Fiber Layer Thickness: The Singapore Epidemiology of Eye Diseases (SEED) Study. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1813.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Recent genome-wide association studies (GWAS) have identified several genes associated with glaucoma, but their role in its pathogenesis is unclear. This study aims to investigate the association between identified glaucoma risk genes and parapapillary retinal nerve fiber layer (pRNFL) thickness.

Methods : A cross-sectional study was conducted with subjects from the three major ethnic groups – Malay, Indian and Chinese – in Singapore. Subjects underwent ocular examinations and pRNFL thickness was measured using spectral-domain optical coherence tomography (SD-OCT). 28 glaucoma-associated SNPs from 14 loci were identified from previous GWAS. Multivariable linear regression with additive genetic model was performed to evaluate the association between the risk variants and pRNFL adjusted for age, sex, genetic principal component and axial length.

Results : 7,125 eyes from 3,877 subjects were included for analysis. Among the risk genes, only SIX6 was associated with reduction in pRNFL thickness. Within SIX6, 4 SNPs were associated with reduction of average pRNFL thickness, including rs33912345 (β= -1.09, p = 1.5 x 10-5), rs10483727 (β= -1.01, p = 6.1 x 10-5), rs34935520 (β= -0.99, p = 1.1 x 10-4) and rs4436712 (β= -1.00, p = 1.2 x 10-4). The association of rs33912345, the most significant SIX6 SNP, with RNFL thickness was strongest in Chinese (β= -1.19, p = 7.2 x 10-3), followed by Indian (β= -0.91, p = 0.014) and Malay (β= -1.22, p = 0.025) population. All of the SIX6 risk alleles were also significantly associated with reduction in superior and inferior quadrant of RNFL (P< 0.001). No other glaucoma risk SNPs was associated with RNFL thickness after Bonferroni correction.

Conclusions : Although the significant SIX6 risk variants were in high linkage disequilibrium (R2 > 0.8), they were reported to be associated with different glaucoma traits. Our study further showed that several SIX6 risk variants were associated with reduction in RNFL thickness. The effects of other glaucoma risk SNPs on RNFL thickness appear to be weak.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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