World-wide Replication And Meta-Analysis Study Confirms Association Of 15q14 Locus With Myopia

Abstract

Purpose: : Myopia is a complex genetic disorder and the most common cause of blindness among adults of working age. Genome-wide association studies have identified susceptibility loci on chromosome 15q14 and 15q25 in Caucasian study populations of European ancestry. We assessed whether these loci are also associated with myopia occurring in other populations.

Methods: : We conducted a confirmation and meta-analysis study in 31 cohorts from 4 different continents. The total study population consisted of 55,167 individuals: 42,835 Caucasians and 12,332 Asians. We performed a meta-analysis of 14 SNPs on 15q14 and 5 SNPs on 15q25 using linear regression analysis with spherical equivalent (SE) as a quantitative outcome and adjusted for age and sex. We calculated the odds ratio of myopia (SE ≤ -3 D) versus hyperopia (SE ≥ +3 D) for carriers of the top-SNP using a random effects meta-analysis.

Results: : At locus 15q14, all SNPs were significantly replicated, with the lowest P-value 3.87 x 10^-12 for SNP rs634990 in Caucasians, and 9.65 x 10^-4 for rs8032019 in Asians. The overall meta-analysis provided P-value 9.20 x 10^-23 for top-SNP rs634990. The odds ratio of myopia versus hyperopia was 1.84 (95% CI 1.60, 2.12) for homozygous carriers of the risk allele at top-SNP rs634990, and 1.34 (95% CI 1.18, 1.51) for heterozygous carriers. SNPs at locus 15q25 did not significantly replicate in Caucasian and Asian populations; the meta-analysis provided P 1.22 x 10^-4 for top-SNP rs939661.

Conclusions: : Common variants at 15q14 influence susceptibility for myopia in Caucasian and Asian populations around the world.

Keywords: myopia • gene mapping • refractive error development