title: Education influences the association between genetic variants and refractive error: a meta-analysis of five Singapore studies.
abstract: Refractive error is a complex ocular trait governed by both genetic and environmental factors and possibly their interplay. Thus far, data on the interaction between genetic variants and environmental risk factors for refractive errors are largely lacking. By using findings from recent genome-wide association studies, we investigated whether the main environmental factor, education, modifies the effect of 40 single nucleotide polymorphisms on refractive error among 8461 adults from five studies including ethnic Chinese, Malay and Indian residents of Singapore. Three genetic loci SHISA6-DNAH9, GJD2 and ZMAT4-SFRP1 exhibited a strong association with myopic refractive error in individuals with higher secondary or university education (SHISA6-DNAH9: rs2969180 A allele, β = -0.33 D, P = 3.6 × 10(-6); GJD2: rs524952 A allele, β = -0.31 D, P = 1.68 × 10(-5); ZMAT4-SFRP1: rs2137277 A allele, β = -0.47 D, P = 1.68 × 10(-4)), whereas the association at these loci was non-significant or of borderline significance in those with lower secondary education or below (P for interaction: 3.82 × 10(-3)-4.78 × 10(-4)). The evidence for interaction was strengthened when combining the genetic effects of these three loci (P for interaction = 4.40 × 10(-8)), and significant interactions with education were also observed for axial length and myopia. Our study shows that low level of education may attenuate the effect of risk alleles on myopia. These findings further underline the role of gene-environment interactions in the pathophysiology of myopia.
authors.affiliation: Saw Swee Hock School of Public Health.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Fan
authors.forename: Robert
authors.initials: R
authors.lastname: Wojciechowski
authors.forename: M
authors.initials: M
authors.lastname: Kamran Ikram
authors.forename: Ching-Yu
authors.initials: CY
authors.lastname: Cheng
authors.forename: Peng
authors.initials: P
authors.lastname: Chen
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
authors.forename: Chen-Wei
authors.initials: CW
authors.lastname: Pan
authors.forename: Chiea-Chuen
authors.initials: CC
authors.lastname: Khor
authors.forename: E-Shyong
authors.initials: ES
authors.lastname: Tai
authors.forename: Tin
authors.initials: T
authors.lastname: Aung
authors.forename: Tien-Yin
authors.initials: TY
authors.lastname: Wong
authors.forename: Yik-Ying
authors.initials: YY
authors.lastname: Teo
authors.forename: Seang-Mei
authors.initials: SM
authors.lastname: Saw
mesh_terms: D056444:Axonemal Dyneins / Q000235:genetics*; D017630:Connexins / Q000235:genetics*; D004522:Educational Status; D059647:Gene-Environment Interaction; D056426:Genetic Loci; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012030:Refractive Errors / Q000209:etiology / Q000235:genetics* / Q000473:pathology*; D012307:Risk Factors; D012846:Singapore; D000097004:Gap Junction delta-2 Protein; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D056444:Axonemal Dyneins; D017630:Connexins; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D000097004:Gap Junction delta-2 Protein; C117636:SFRP1 protein, human; D000094742:Secreted Frizzled-Related Proteins; C430745:DNAH9 protein, human