Among them, it is noteworthy that two largest GWAS of myopia and refractive error, reported by 23andMe and Consortium for Refractive Error and Myopia (CREAM) [7, 8], discovered coincidentally a number of significant genome-wide associations, including the novel KCNQ5 gene with functions in ion transport.
KCNQ5 (potassium voltage-gated channel KQT-like subfamily, member 5), identified as myopia-related gene for the first time, encodes a potassium channel found in the retinal pigment epithelium (RPE) and neural retina.
Tag SNPs of KCNQ5 gene were sourced from the HapMap database (release 27/phases II + III on NCBI Build 36 assembly dbSNPb126).
The allelic frequencies and association analysis of KCNQ5 gene polymorphisms between cases and controls are summarized in Table 2.
Haplotypic analyses were performed here to help understand the effects of KCNQ5 gene polymorphisms on the manifestation of high myopia.
Moreover, we examined the haplotype windows with the most significant result of omnibus association analysis for KCNQ5 (Table 5).
This study provides new evidence of associations between potassium channel gene KCNQ5 and high myopia susceptibility.
KCNQ5 (K [v.sub.7.5]) gene is a member of the potassium voltage-gated channel KCNQ/K[v.sub.7] gene family and is known to mediate the M-type potassium current in some excitable cells including retinal pigment epithelium (RPE) cells [12, 21].
KCNQ5 gene is located at chromosome position 6q13, which is a potential locus associated with myopia susceptibility .
In the present study, KCNQ5 gene was found to be associated with high myopia in a Southern Chinese population, consistent with the results of CREAM and 23andMe [7, 8].We further demonstrated significant differences in the distribution of allele and genotype frequencies between high myopia and control groups for all five SNPs selected which remained significant after correction for multiple testing by permutations.
As a result, five SNPs in KCNQ5 gene showed significant differences in distribution of haplotypes between cases and controls.
The five SNPs under study are located in an intron of KCNQ5. Although introns are noncoding regions of DNA where the vast majority (over 90%) of variants associated with complex phenotypes have been detected , they may be involved in the underlying pathogenic mechanism by regulating mRNA expression.