Genome-Wide Association Study Identifies a Locus and Candidate Gene for Refractive Errors and Myopia in the General Population

Abstract

Purpose: : Refractive errors are the most common ocular disorders worldwide. Myopia occurs in one third of the population, and may lead to irreversible blindness. To date, identification of common genetic variants influencing this trait has been challenging.

Methods: : We conducted a genome-wide association study testing 2.5 million single nucleotide polymorphisms (SNP) for association with refractive error in 5,328 unrelated individuals of a Dutch population-based study using a quantitative trait loci approach. Refractive error was measured with Topcon RM-A2000 autorefractor, and analyzed as spherical equivalent. We replicated findings in four independent Caucasian cohorts (10,280 persons).

Results: : We identified a significant association with a locus on chromosome 15. The association with the most significant SNP was P=1.78*10^-15. The minor allele of this variant increased the risk of myopia, and protected against hyperopia [OR 1.89 (95% CI 1.46, 2.45) of myopia versus hyperopia]. The associated region lies proximal to a gene which is highly expressed in the retina and which regulates signal transmission.

Conclusions: : Our findings suggest that this gene is important in the pathogenesis of refractive errors in the general population.

Keywords: myopia • gene mapping • refractive error development