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Qiao Fan, Virginie JM Verhoeven, Robert Wojciechowski, Ching-Yu Cheng, Pirro G Hysi, Christopher J Hammond, Seang-Mei Saw, Caroline C W Klaver, ; Genome-wide joint meta-analyses of SNP and its interaction with education identify novel loci for refractive error in CREAM. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4515.
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© ARVO (1962-2015); The Authors (2016-present)
This study aims to identify genes that are associated with myopia by considering the interactions with education, a major environmental factor for myopia, using genome-wide single nucleotide polymorphism (SNP) data in the Consortium for Refractive Error and Myopia (CREAM).
We conducted genome-wide joint meta-analyses in CREAM to simultaneously test both the genetic effects and interaction between each genetic variant and education on refractive error, including 25,836 adults of European ancestry from 14 studies in Europe, Australia and US, and 9,076 adults from 8 Asian studies. Refractive error was measured by autorefraction. Spherical equivalent (SE) was calculated and analyzed as a quantitative trait. Education was categorized as higher secondary or university education versus lower secondary education or below. After stringent quality control filters, the genotypes of each cohort were imputed using the 1000 genome reference panels. For each study, the linear regression model included SNP, education and SNP × education terms to allow for SNP and education interaction effects, adjusting for age, sex and top principal components.
We identified hundreds of SNPs exceeding genome-wide significance, clustered at 8 novel and 7 known loci, associated with SE (lowest joint meta P value = 3.91 × 10-15). Among these novel loci, regions at chromosome 8, 12 and 15 exhibited both interaction effects with education (lowest P value for interaction = 7.74 × 10-3) and SNP main effects (lowest P value for SNP effect = 7.76 × 10-11). Effects of SNP × education interaction on SE tended to be larger in Asian populations than in Caucasians at all the identified loci, with the heterogeneity for interaction present at three loci (P value for heterogeneity < 0.01). The identified novel loci, including collagen genes and neurotransmitter receptors, are within the biological context of the visually evoked signaling pathway.
This represents the largest genome-wide joint meta-analysis of gene-by-education interaction on refractive error to date in multiple ancestral populations. The discovery of these loci will aid further characterization of the role of the gene and environmental interaction in understanding the heterogeneity of myopia etiology.
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