Update on the Epidemiology and Genetics of Myopic Refractive Error

Justin C Sherwin; David A Mackey


Expert Rev Ophthalmol. 2013;8(1):63-87. 

In This Article

Five-year View

Ophthalmic genetics is evolving rapidly and we will understand much more about the etiology of myopic refractive error over the next 5 years. Much will be achieved with the advent of new technology. The emergence of GWAS that have underpinned the discovery of variants associated with low/moderate and, more commonly, high myopia has been a major advance. Increasingly, collaboration between research groups is required for the discovery, validation and meta-analysis of genetic discoveries from GWAS. Such collaborations also vastly increase the sample sizes available – crucial for ensuring sufficient power for finding rare variants, copy number variants, SNPs of modest effect and evidence of gene–gene interaction. Chromosomal regions that have been previously identified for myopia through linkage analysis will be amenable to new-generation sequencing, thus obviating the requirement for comprehensive SNP analysis.[212]

Epigenetics seeks to understand heritable changes in gene expression that cannot be attributed to changes in primary DNA nucleotide sequence. From this angle, it may be possible to further elucidate the etiology of complex non-Mendelian disease and to assist in developing therapeutic interventions.[213] One key mechanism involves methylation of cytosine–phosphate–guanine sites. It is likely that epigenetic effects play an important role in the etiology of myopic refractive error, and will be instrumental in exploring possible gene–environment interactions.[214] Now the role of such studies remains largely undefined. An example of an epigenetic approach to myopia research has demonstrated that hypermethlyation of cytosine–phosphate–guanine sites promoter/exon 1 of the COL1A1 gene may be associated with reduced collagen synthesis in myopic scleras.[215]

Proteomic approaches could potentially use aqueous or vitreous humor, tears or serum to identify biomarkers of myopia. Duan et al. performed a proteomic analysis by comparing the protein composition of the aqueous humor of highly myopic eyes to nonmyopic eyes with cataract.[216] Interestingly, total protein concentration in the aqueous humor of highly myopic eyes was significantly greater than in controls. Analysis linked the higher protein concentration to albumin, transthyretin and a vitamin D-binding protein; these proteins may represent biomarkers that are involved in axial elongation. One limitation of proteomic analysis is the potential confounding effect of concurrent medical and/or surgical treatments, as they may also influence protein composition of the tissues under investigation.