Genetic Association of Insulin-like Growth Factor-1 Polymorphisms with High-Grade Myopia in an International Family Cohort

PURPOSE. Evidence from human myopia genetic mapping studies (MYP3 locus), modulated animal models, and observations of glycemic control in humans suggests that insulin-like growth factor (IGF)-1 plays a role in the control of eye growth. This study was conducted to determine whether IGF-1 polymorphisms are associated with myopia in a large, international dataset of Caucasian high-grade myopia pedigrees. METHODS. Two hundred sixty-five multiplex families with 1391 subjects participated in the study. IGF-1 genotyping was performed with 13 selected tag single nucleotide polymorphisms (SNPs) using allelic discrimination assays. A family-based pedigree disequilibrium test (PDT) was performed to test for association. Myopia status was defined using sphere (SPH) or spherical equivalent (SE), and analyses assessed the association of (1) high-grade myopia (<= -5.00 D), and (2) any myopia (<= -0.50 D) with IGF-1 markers. Results were declared significant at P <= 0.0038 after Bonferroni correction. Q values that take into account multiple testing were also obtained. RESULTS. In all, three SNPs-rs10860860, rs2946834, and rs6214-were present at P < 0.05. SNP rs6214 showed positive association with both the high-grade-and any-myopia groups (P = 2 x 10(-3) and P = 2 = 10 = 3, respectively) after correction for multiple testing. CONCLUSIONS. The study supports a genetic association between IGF-1 and high-grade myopia. These findings are in line with recent evidence in an experimental myopia model showing that IGF-1 promotes ocular growth and axial myopia. IGF-1 may be a myopia candidate gene for further investigation. (Invest Ophthalmol Vis Sci. 2010;51:4476-4479) DOI:10.1167/iovs.09-4912