Rs524952

rs524952 is a single nucleotide variant found on chromosome 15q14 (near the GJD2 gene) that has been implicated in myopia. In humans, the A allele has generally been associated with lower odds of myopia compared to the T (minor) allele. Myopia is characterized by abnormal elongation of the eyeball, which causes light to be focused at a point in front of the retina. Approximately 30% of the U.S. population is afflicted with myopia (https://www.nei.nih.gov/news/briefs/myopia). Myopia is particular prevalent in Asia, where 90% of pre-college students are estimated to have acquired it. The GJD2 gene encodes a gap junction protein (connexin) in neuronal cells in the retina, which allows the exchange of small molecules and ions across the membrane. It is involved in neurotransmission at the retina and GJD2 knockout mice have been shown to suffer from retinal photoreception defects.

In 2010, a study by Solouki et al. was conducted on 5,328 Dutch individuals by genotyping approximately 2.5 million autosomal SNPs. The rs524952 A allele was reported to have a slightly higher odds of myopia (β = 0.25, P = 1.03 × 10−7). However, in the meta-analysis conducted on 15,608 individuals, the rs524952 A allele was reported to have an β of –0.23 (P = 1.03 × 10−14). Given that β is the log-odds ratio, this translates to an odds ratio of 0.795, using the T allele as reference.

In 2011, Hayashi et al. reported a study on 1,125 Japanese patients with high myopia and 929 healthy Japanese patients. The case-control study was done on 4 SNPs, and the SNP rs524952 was found to be strongly associated with myopia (P = 1.62 × 10−6). In contrast to other studies, the rs524952 A allele was found to increase the odds of myopia (OR = 1.37). In 2012, Jiao et al. studied five SNPs at chromosome 15q14, across 608 university students at Guangzhou. 300 of the students had high myopia, while the remaining 308 did not have refractive error. rs524952 was found to be strongly associated with high myopia, with the T allele having an odds ratio of 1.78 (P < 8.8×10−7). Using the T allele as reference, the A allele had an odds ratio of 0.56.

In 2013, a large-scale study by Verhoeven et al. was done on 37,382 individuals of European ancestry. Approximately 2.5 million autosomal SNPs were studied, and 309 SNPs passed the genome-wide significance threshold of P = 5.0 × 10−8. The best 18 SNPs were then studied in 8,376 Asian individuals, where rs524952 was found to be the most significantly associated SNP. In the combined study (n = 45, 758), the rs524952 A allele had a β of –0.158 (P = 1.44 × 10−15). This translates to an odds ratio of 0.853.

In 2014, Fan et al. conducted a meta-analysis using five studies based on individuals from Singapore to investigate the effects of education level on the genetic significance of previously identified SNPs. A set of 40 candidate SNPs were used (including rs524952), and the 8,461 individuals were stratified into a higher education group (higher secondary or university education) and a lower education group (below lower secondary). rs524952 was found to have a higher significance (β = –0.31, P = 1.68 × 10−5) in individuals who attained higher education than those who attained a lower level of education (β = –0.08, P = 0.041). In the interaction model of SNP and education level, rs524952 had a β of –0.23 with P = 0.0038. In all three cases, the rs524952 A allele was found to have lower odds of myopia than the T allele.