Abstract
Myopia, commonly referred to as nearsightedness, is one of the most common causes of visual disability throughout the world. It affects more people worldwide than any other chronic visual impairment condition. Although the prevalence varies among various ethnic groups, the incidence of myopia is increasing in all populations across globe. Thus, it is considered a pressing public health problem. Both genetics and environment play a role in development of myopia. To elucidate the epigenetic mechanism(s) underlying the pathophysiology of high-myopia, we conducted methylation profiling in 18 cases and 18 matched controls (aged 4–12 years), using Illumina MethylationEPIC BeadChips array. The degree of myopia was variable among subjects, ranging from −6 to −15D. We identified 1541 hypermethylated CpGs, representing 1745 genes (2.0-fold or higher) (false discovery rate (FDR) p ≤ 0.05), multiple CpGs were p < 5 × 10−8 with a receiver operating characteristic area under the curve (ROC-AUC) ≥ 0.75 in high-myopia subjects compared to controls. Among these, 48 CpGs had excellent correlation (AUC ≥ 0.90). Herein, we present the first genome-wide DNA methylation analysis in a unique high-myopia cohort, showing extensive and discrete methylation changes relative to controls. The genes we identified hold significant potential as targets for novel therapeutic intervention either alone, or in combination.
Highlights
Myopia, or nearsightedness, the most prevalent form of refractive error, is caused by excessive axial elongation of the eye as a major mechanism in children[1]
We identified 1541 CpG sites in 1745 unique genes that were differentially methylated (2.0-fold or higher) in high myopia subjects compared to controls without high myopia
The detailed list of the most significant differentially methylated CpG sites based on false discovery rate (FDR)-corrected p-values, fold change and area under the curves (AUCs) for high myopia detection is shown in Supplementary Table S1
Summary
Nearsightedness, the most prevalent form of refractive error, is caused by excessive axial elongation of the eye as a major mechanism in children[1]. A recent study by Holden et al estimated the huge growth in the world population of myopia and high myopia, defined in his study as loss of 6.00 diopters (D) or more, as an increase from 1406 million and 163 million in 2000 to 4758 million and 938 million in 2050, for the two forms respectively[4]. Environmental factors along with genetic predisposition are associated with the increasing prevalence of myopia amongst children, the mechanism through which they act is moderately understood. An epigenetic event such as DNA methylation could be one of the mechanisms through which these environmental factors influence the development of myopia. To elucidate potential epigenetic mechanism(s) underlying the pathophysiology of high myopia, we conducted a genome-wide methylation analysis on 18 high myopia subjects and an equal number of controls
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
