Genome-wide analysis points to roles for extracellular matrix remodeling, the visual cycle, and neuronal development in myopia

TL;DR

This large genome-wide study identifies multiple genetic factors and mechanisms, including extracellular matrix remodeling and neuronal development, that contribute to the development of myopia in humans.

Contribution

It is the largest GWAS on myopia in Europeans, revealing 19 significant genetic associations and suggesting complex interactions in myopia development.

Findings

19 genetic associations linked to myopia onset

Genes involved in extracellular matrix and neuronal development identified

Multiple mechanisms contribute to myopia etiology

Abstract

Myopia, or nearsightedness, is the most common eye disorder, resulting primarily from excess elongation of the eye. The etiology of myopia, although known to be complex, is poorly understood. Here we report the largest ever genome-wide association study (43,360 participants) on myopia in Europeans. We performed a survival analysis on age of myopia onset and identified 19 significant associations (p < 5e-8), two of which are replications of earlier associations with refractive error. These 19 associations in total explain 2.7% of the variance in myopia age of onset, and point towards a number of different mechanisms behind the development of myopia. One association is in the gene PRSS56, which has previously been linked to abnormally small eyes; one is in a gene that forms part of the extracellular matrix (LAMA2); two are in or near genes involved in the regeneration of 11-cis-retinal (RGR and RDH5); two are near genes known to be involved in the growth and guidance of retinal ganglion cells (ZIC2, SFRP1); and five are in or near genes involved in neuronal signaling or development. These novel findings point towards multiple genetic factors involved in the development of myopia and suggest that complex interactions between extracellular matrix remodeling, neuronal development, and visual signals from the retina may underlie the development of myopia in humans.