June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Genetic susceptibility to open angle glaucoma: the Blue Mountains Eye Study
Author Affiliations & Notes
  • Linda Zheng
    Centre for Vision Research, Westmead Millennium Institute, Sydney, NSW, Australia
  • Annette Kifley
    Centre for Vision Research, Westmead Millennium Institute, Sydney, NSW, Australia
  • Jie Jin Wang
    Centre for Vision Research, Westmead Millennium Institute, Sydney, NSW, Australia
  • Andrew JR White
    Centre for Vision Research, Westmead Millennium Institute, Sydney, NSW, Australia
    Ophthalmology, University of Sydney, Sydney, NSW, Australia
  • Kathryn P Burdon
    Menzies Institute for Medical Research, Hobart, TAS, Australia
  • Jamie E Craig
    Ophthalmology, Flinders University, Adelaide, SA, Australia
  • Stuart MacGregor
    Genetic Epidemiology, Molecular Epidemiology and Neurogenetics Laboratories, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
  • Paul Mitchell
    Centre for Vision Research, Westmead Millennium Institute, Sydney, NSW, Australia
    Ophthalmology, University of Sydney, Sydney, NSW, Australia
  • Paul R Healey
    Centre for Vision Research, Westmead Millennium Institute, Sydney, NSW, Australia
    Ophthalmology, University of Sydney, Sydney, NSW, Australia
  • Footnotes
    Commercial Relationships Linda Zheng, None; Annette Kifley, None; Jie Jin Wang, None; Andrew White, None; Kathryn Burdon, None; Jamie Craig, None; Stuart MacGregor, None; Paul Mitchell, None; Paul Healey, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 3684. doi:
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    • Get Citation

      Linda Zheng, Annette Kifley, Jie Jin Wang, Andrew JR White, Kathryn P Burdon, Jamie E Craig, Stuart MacGregor, Paul Mitchell, Paul R Healey; Genetic susceptibility to open angle glaucoma: the Blue Mountains Eye Study. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3684.

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

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Abstract
 
Purpose
 

Six single nucleotide polymorphisms (SNPs); rs4656461 (TMCO1), rs4619890 (AFAP1), rs11969985 (GMDS), rs4977756 (CDKN2B_AS1), rs2472493 (ABCA1) and rs10483727 (SIX1/SIX6); have recently been reported to be associated with the development of primary open angle glaucoma (OAG). We aimed to determine whether these risk alleles are independently associated with an increased risk of primary open angle glaucoma (POAG) in at least one eye in the Blue Mountains Eye Study (BMES) cohort, and evaluate genetic risk scores for POAG.

 
Methods
 

OAG diagnosis by expert panel was based on masked glaucomatous visual field loss and matching optic disc appearance, independent of intraocular pressure. Genetic analysis was performed using Illumina HumanHap670 quad arrays. Logistic regression models were used to assess associations between the genetic loci and POAG, adjusting for age and gender. Risk scores were constructed quantifying the effect of each additional risk allele among SNPs significant together in multivariable modeling.

 
Results
 

A total of 2481 participants in the BMES cohort had data on SNPs and glaucoma status. Of these, 85 had POAG (cases) and 2396 did not (controls).<br /> <br /> When analyzed individually, four SNPs, rs4656461 (risk allele G), rs4977756 (risk allele A), rs10483727 (risk allele A) and rs2472493 (risk allele G) all conferred increased risk of OAG (p=0.047, 0.004, 0.04 and 0.006 respectively) (Table 1). Corresponding risk allele frequencies were 0.12, 0.60, 0.39 and 0.43.<br /> <br /> In multivariable modeling, 3 SNPs (rs4656461, rs4977756 and rs2472493) remained significantly associated with OAG (OR 1.61-1.67, p<0.05). These effects appeared largely independent of each other. Proportions of participants developing OAG were 1.7%, 2.7%, 4.3% or 6.0% among those carrying 0-1, 2, 3 or 4-6 risk alleles from these three SNPs.

 
Conclusions
 

These recently discovered SNPs were associated with OAG in a European-derived older population, each conferring about a 50% increased risk. Increasing number of risk alleles was associated with increasing glaucoma risk in a dose-dependent manner. Genetic risk scoring may have clinical utility by providing a glaucoma-enriched population for screening.  

 
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