April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
A Genome-Wide Association Study of Glaucomatous Optic Neuropathy
Author Affiliations & Notes
  • W. D. Ramdas
    Erasmus Medical Center, Rotterdam, The Netherlands
  • L. M. E. van Koolwijk
    The Rotterdam Eye Hospital, Rotterdam, The Netherlands
  • M. K. Ikram
    Erasmus Medical Center, Rotterdam, The Netherlands
  • H. G. Lemij
    The Rotterdam Eye Hospital, Rotterdam, The Netherlands
  • R. C. W. Wolfs
    Erasmus Medical Center, Rotterdam, The Netherlands
  • P. T. V. M. de Jong
    The Netherlands Institute for Neuroscience (NIN-KNAW), Amsterdam, The Netherlands
  • N. M. Jansonius
    University Medical Center Groningen, Groningen, The Netherlands
  • J. R. Vingerling
    Erasmus Medical Center, Rotterdam, The Netherlands
  • C. C. W. Klaver
    Erasmus Medical Center, Rotterdam, The Netherlands
  • C. M. van Duijn
    Erasmus Medical Center, Rotterdam, The Netherlands
  • Footnotes
    Commercial Relationships  W.D. Ramdas, None; L.M.E. van Koolwijk, None; M.K. Ikram, None; H.G. Lemij, None; R.C.W. Wolfs, None; P.T.V.M. de Jong, None; N.M. Jansonius, None; J.R. Vingerling, None; C.C.W. Klaver, None; C.M. van Duijn, None.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 2157. doi:
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      W. D. Ramdas, L. M. E. van Koolwijk, M. K. Ikram, H. G. Lemij, R. C. W. Wolfs, P. T. V. M. de Jong, N. M. Jansonius, J. R. Vingerling, C. C. W. Klaver, C. M. van Duijn; A Genome-Wide Association Study of Glaucomatous Optic Neuropathy. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2157.

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

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Abstract

Purpose: : Genetic determinants of open-angle glaucoma and one of its quantitative markers, the vertical cup-to-disc ratio (VCDR), remain largely undetermined. To identify genetic variants of VCDR we performed a genome-wide association study and related our findings to glaucoma.

Methods: : The gene discovery included 7360 unrelated individuals from the population-based Rotterdam Study I and Rotterdam Study II cohorts. Findings were replicated in two independent Dutch cohorts including 3612 Caucasian persons and a series of 428 open-angle glaucoma patients. The analyses included 2.5 million genotyped and imputed single nucleotide polymorphisms (SNPs).

Results: : We found two genome-wide significant loci for VCDR, one on chromosome 9p21 (p=6.15x10-11) and one on chromosome 14q22.3-q23 (p=2.93x10-10. Both loci were replicated in the independent cohorts and were associated with open-angle glaucoma (odds ratio [OR] heterozygotes 0.69 (p=0.002), OR homozygotes 0.46 (p=2.43x10-6) for the locus on chromosome 9p21, and 1.77 (p=2.69x10-5) for homozygotes for the locus on chromosome 14q22.3-q23. Meta-analyses of all four cohorts revealed four other genome-wide significant loci on chromosomes 10q21.3-q22.1, 11q13, 13q13 and 22q12.1. Of these loci, only the locus on chromosome 10q21.3-q22.1 was marginally associated with open-angle glaucoma (OR=1.27; p=0.039).

Conclusions: : We found three novel genes implicated consistently in open-angle glaucoma and a consistent genome-wide significant evidence for six VCDR loci. These results potentially provide insight into the biological mechanisms that underlie open-angle glaucoma.

Keywords: genetics • optic nerve • optic disc 
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