In the United States and Europe, 30% to 50% are nearsighted (meaning you can’t see far distances), whereas, in parts of East Asia, nearsighted currently affects most young adults. Nearsighted (known as myopia) generally results from excessive axial growth of the eye during childhood, leading to a mismatch between the optical focal length of the eye and the axial length of the eye. This structural relationship between excessive axial eye length and refractive error gives rise to the rule of thumb that elongation of 1mm can cause a shift in vision by a specific amount, helping optometrists choose the right glasses or contact prescription for someone. However, this axial elongation can also contribute to other eye sight issues.
In a previous study of a chick model, the genetic variants regulating eye size in eyes with normal visual experience were found to be distinct from the genetic variants conferring susceptibility to myopia induced by altered visual experience. Although a handful of studies in humans have each identified one or a few gene variants that fit this pattern (i.e., being associated with eye size but not associated with refractive error), the generality of this distinction has never been tested in humans. Here, researchers perform the first genome-wide association study (GWAS) for eye size in humans and use the results to test the hypothesis that the genetic variants controlling normal eye size do not overlap with those associated with susceptibility to refractive error.
In this study, the eyes of UK Biobank participants were classified as emmetropic (people having no eyesight issues) by using specific spherical (SPH) and astigmatic (CYL) measurements. . Ideally, a GWAS for axial length, or axial length and corneal curvature combined, would have served as a better GWAS for eye size; however, a very large, genetically profiled cohort with axial length measurements does not exist yet. Thus, this study performed a GWAS for corneal curvature in the group as a proxy for eye size. After testing 6,961,902 genetic markers in a sample of 22,180 UK Biobank participants, a total of 32 independent genetic regions harbored markers that were significantly associated with corneal curvature in emmetropes, which include rs4074961 in the RSPO1 gene, rs1550094 in the PRSS56 gene, rs1309572 in the CWC27 gene, rs6787409 in the PPP2R3A gene, rs7723567 in the THBS4 gene, rs11836781 in the LOC105369896 gene and rs3118515 in the LOC100506532 gene. In addition, analysis for genetic correlation between the eye size surrogate and a series of other traits: refractive error, corneal curvature, and body height based on a set of over 1 million genetic variants distributed across the genome. It showed eye size and corneal curvature were well correlated. Most importantly, the genetic correlation between eye size and refractive error was close to zero, suggesting that genetic variants regulating eye size in emmetropic eyes may not be related to susceptibility to myopia.
The major weakness of the current work was that they had to use those with ineffective eyesight as a proxy for eye size rather than a dataset with information on both eyes size and eyesight. However, in support of the validity of this approach, a proportion of the most strongly associated variants in the current GWAS were in genomic regions previously reported to be associated with eye size (or with both axial length and corneal curvature). If you would like to know more about this research, you can read the study here:
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