April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
Genome-Wide Association Study (GWAS) of Age-Related Macular Degeneration (AMD) in Asian Malays: The Singapore Malay Eye Study (SiMES)
Author Affiliations & Notes
  • B. K. Cornes
    Singapore Eye Research Institute, Singapore, Singapore
  • E. Tai
    Centre for Molecular Epidemiology,
    Department of Medicine,
    National University of Singapore, Singapore, Singapore
  • W. Tay
    Singapore Eye Research Institute, Singapore, Singapore
  • X. SIM
    Centre for Molecular Epidemiology,
    National University of Singapore, Singapore, Singapore
  • M. Seielstad
    Genome Institute of Singapore, Singapore, Singapore
  • J. Wang
    Centre for Vision Research, University of Sydney, Sydney, Australia
    Centre for Eye Research, University of Melbourne, Melbourne, Australia
  • P. Mitchell
    Centre for Vision Research, University of Sydney, Sydney, Australia
  • E. L. Lamoureux
    Singapore Eye Research Institute, Singapore, Singapore
    Centre for Eye Research, University of Melbourne, Melbourne, Australia
  • S. Saw
    Singapore Eye Research Institute, Singapore, Singapore
    Department of Epidemiology and Public Health, Yong Loo Lin School of Medicine,
    National University of Singapore, Singapore, Singapore
  • T. Y. Wong
    Singapore Eye Research Institute, Singapore, Singapore
    Centre for Eye Research, University of Melbourne, Melbourne, Australia
  • Footnotes
    Commercial Relationships  B.K. Cornes, None; E. Tai, None; W. Tay, None; X. Sim, None; M. Seielstad, None; J. Wang, None; P. Mitchell, None; E.L. Lamoureux, None; S. Saw, None; T.Y. Wong, None.
  • Footnotes
    Support  This study was supported by the National Medical Research Council Grants No 0796/2003 and STaR/0003/2008
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 1272. doi:
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      B. K. Cornes, E. Tai, W. Tay, X. SIM, M. Seielstad, J. Wang, P. Mitchell, E. L. Lamoureux, S. Saw, T. Y. Wong; Genome-Wide Association Study (GWAS) of Age-Related Macular Degeneration (AMD) in Asian Malays: The Singapore Malay Eye Study (SiMES). Invest. Ophthalmol. Vis. Sci. 2010;51(13):1272.

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

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Abstract

Introduction: : Aim: To understand the role of known common genetic variants associated with AMD in an urban Malay population.

Methods: : We conducted a population-based case-control GWAS of AMD in Singaporean Malay participants aged between 40-80 years from a well characterised population-based study: the Singapore Malay Eye Study (SiMES). Early and late AMD signs were graded from retinal photographs using the Wisconsin grading system.

Results: : Of the 3280 participants who were examined (78.7%), 3265 had photographs of sufficient quality for grading of AMD signs; of these, 3072 also had DNA available and were genotyped using the Illumina Human610-Quad BeadChips. 530 samples were excluded due to high missingness, excess heterozygosity, cryptic relatedness, discordant ethnicity or gender discrepancy, leaving a total of 140 AMD cases (123 early, 17 late) and 2390 controls. No association reaching genome-wide significance (p<5x10-8) was found. However, several SNPs showed suggestive associations (p-values between 5x10-8 and 5x10-4). Of the known SNPs associated with AMD, rs680638 on chromosome 1 (near HMCN1) (p=3.67x10-2; additive OR: 0.75 [95%CI: 0.58-0.98] for risk allele T) and rs10490924 on chromosome 10 (upstream of genes LOC387715 and HTRA1) (p=1.48x10-2; additive OR: 1.36 [95%CI: 1.06-1.74] for risk allele T) were associated with AMD in this Malay sample. Direction of association was different for rs680638 but the same for rs10490924 to prior studies. rs547154, on chromosome 6 (near C2), showed a borderline association (p=8.08x10-2; additive OR: 0.69 [95%CI: 0.45-1.05] for risk allele T) in the same direction to previous findings.

Conclusions: : In this population, we replicated associations of some previously implicated AMD SNPs, particularly those identified in Chinese and Japanese. Our findings suggest that some genetic associations to AMD are ethnicity-specific. Alternatively, failure to find significant associations may be due to insufficient power, particularly with the low number of AMD cases. Observed regions of suggestive associations are of interest for future replication studies.

Keywords: age-related macular degeneration • gene mapping • clinical (human) or epidemiologic studies: biostatistics/epidemiology methodology 
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