Abstract
BackgroundMyopia is the most common ocular disorder worldwide and imposes tremendous burden on the society. It is a complex disease. The MYP6 locus at 22 q12 is of particular interest because many studies have detected linkage signals at this interval. The MYP6 locus is likely to contain susceptibility gene(s) for myopia, but none has yet been identified.Methodology/Principal FindingsTwo independent subject groups of southern Chinese in Hong Kong participated in the study an initial study using a discovery sample set of 342 cases and 342 controls, and a follow-up study using a replication sample set of 316 cases and 313 controls. Cases with high myopia were defined by spherical equivalent ≤ -8 dioptres and emmetropic controls by spherical equivalent within ±1.00 dioptre for both eyes. Manual candidate gene selection from the MYP6 locus was supported by objective in silico prioritization. DNA samples of discovery sample set were genotyped for 178 tagging single nucleotide polymorphisms (SNPs) from 26 genes. For replication, 25 SNPs (tagging or located at predicted transcription factor or microRNA binding sites) from 4 genes were subsequently examined using the replication sample set. Fisher P value was calculated for all SNPs and overall association results were summarized by meta-analysis. Based on initial and replication studies, rs2009066 located in the crystallin beta A4 (CRYBA4) gene was identified to be the most significantly associated with high myopia (initial study: P = 0.02; replication study: P = 1.88e-4; meta-analysis: P = 1.54e-5) among all the SNPs tested. The association result survived correction for multiple comparisons. Under the allelic genetic model for the combined sample set, the odds ratio of the minor allele G was 1.41 (95% confidence intervals, 1.21-1.64).Conclusions/SignificanceA novel susceptibility gene (CRYBA4) was discovered for high myopia. Our study also signified the potential importance of appropriate gene prioritization in candidate selection.
Highlights
Myopia is present if distant objects are focused in front of, rather than on, the retina
Cases with high myopia were defined by spherical equivalent (SE) #-8.00 D for both eyes, and controls by SE within 61.00 D for both eyes
Within a case-control study framework, subjects were recruited with stringent criteria in the extremes of the visual spectrum
Summary
Myopia is present if distant objects are focused in front of, rather than on, the retina It is the most common eye problem in the world. Often defined as a refractive error of -6.00 dioptres (D) or worse, severely elevates the risk of various degenerative eye diseases and is the leading cause of vision loss or even irreversible blindness [4]. It will potentially impose economic burden on Hong Kong society and working population in the long term. Myopia is the most common ocular disorder worldwide and imposes tremendous burden on the society The MYP6 locus is likely to contain susceptibility gene(s) for myopia, but none has yet been identified
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