Purpose: Two recent large-scale genome-wide association studies identified significant associations between myopia and single nucleotide polymorphisms (SNPs) near the PRSS56, BMP3, KCNQ5, LAMA2, TOX, TJP2, RDH5, ZIC2, RASGRF1, GJD2, RBFOX1, and SHISA6 genes. Our study is to examine whether rare variants in these genes contribute to high myopia.
Methods: Whole-exome sequencing was performed on samples of 298 probands with early-onset high myopia (eoHM; spherical refraction in each meridian ≤ -6.00 [diopters] D in both eyes; age of onset < 7 years) and 195 controls (different forms of retinal degeneration including Leber congenital amaurosis, cone-rod dystrophy, and familial exudative vitroretinopathy). Potential variations in these genes were selected for further validation and comparison to the controls. Moreover, Sanger sequencing was used to evaluate the coding regions and the upstream 800 bps of GJD2 in 395 additional subjects with late-onset moderate to high myopia (loMHM; spherical refraction in each meridian ≤ -4.00 D; age of onset ≥ 7 years) and 403 healthy controls (-0.50 D ± 1.00 D).
Results: Exome sequencing of the 298 probands with eoHM identified 25 rare variants that were predicted to affect coding residues. The segregation analysis and the distribution of rare variants between patients and controls did not provide evidence to support their involvement in myopia. Sanger sequencing of GJD2 in an additional 395 subjects with loMHM and 403 healthy controls did not identify myopia-associated variants.
Conclusions: We did not find evidence to support the association of myopia with rare variants in these genes, probably due to our limited sample size. Additional studies are expected to validate these results.
Keywords: association; candidate genes; exome sequencing; high myopia; variants.
Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.