September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Genome-Wide Association Study Identifies Novel Genes Associated with High Myopia in the General Population
Author Affiliations & Notes
  • Pirro G Hysi
    Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom
  • Virginie JM Verhoeven
    Erasmus University Medical Center, Rotterdam, Netherlands
  • Robert Wojciechowski
    Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States
  • Milly S Tedja
    Erasmus University Medical Center, Rotterdam, Netherlands
  • René Hoehn
    Universitätsmedizin Mainz, Mainz, Germany
  • Caroline C W Klaver
    Erasmus University Medical Center, Rotterdam, Netherlands
  • Christopher J Hammond
    Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom
  • Footnotes
    Commercial Relationships   Pirro Hysi, None; Virginie Verhoeven, None; Robert Wojciechowski, None; Milly Tedja, None; René Hoehn, None; Caroline Klaver, None; Christopher Hammond, None
  • Footnotes
    Support  Fight for Sight UK, Early Career Investigator Award
Investigative Ophthalmology & Visual Science September 2016, Vol.57, No Pagination Specified. doi:
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      Pirro G Hysi, Virginie JM Verhoeven, Robert Wojciechowski, Milly S Tedja, René Hoehn, Caroline C W Klaver, Christopher J Hammond; Genome-Wide Association Study Identifies Novel Genes Associated with High Myopia in the General Population. Invest. Ophthalmol. Vis. Sci. 201657(12):.

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

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Abstract

Purpose : High myopia, an extreme form of refractive error and a common cause of blinding complications is highly heritable. Despite successes in gene discovery, most of refractive error variability remains unexplained. This work aimed at exploring the genetic architecture of high myopia in the general population.

Methods : A meta-analysis of genome-wide association (GWAS) logistic regression results computed in 23 cohorts of European (1930 cases, 4245 controls ) and Asian descent (955 cases, 2216 controls), participating in the Consortium for Refractive Error And Myopia (CREAM) was carried out. The anlyses compared allele dosage variation for each of the more than 10 million polymorphisms present in the 1,000 Genomes Project in high myopic subjects (Spherical Equivalent <6.0 Diopters) versus emmetropes (-0.75D < SE <0.75D), after adjustment for age, sex and population stratification. Results were validated in independent datasets and effect sizes were compared with those observed for quantitatively measured refraction.

Results : Data meta-analysis from all 9,346 subjects identified genome-wide statistically significant association with three novel genomic loci on chromosomes 5, 6 and 10. None of these loci was associated at significant level in previous quantitative analyses of spherical equivalent (p>0.0001). The strongest of these associations (rs9462987, p=5.02x10-09) was within the CDC5L genomic sequence, a gene coding for a transcription activator and involved in cell cycle.
Although not GWAS-significant, most of the loci previously associated with refraction remained moderately associated with high myopia.

Conclusions : These results implicate specific genetic loci associated with high myopia distinct from common myopia. This expands our understanding of genes involved in refractive error pathogenesis.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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