Education interacts with genetic variants near GJD2, RBFOX1, LAMA2, KCNQ5 and LRRC4C to confer susceptibility to myopia

Myopia most often develops during school age, with the highest incidence in countries with intensive education systems. Interactions between genetic variants and educational exposure are hypothesized to confer susceptibility to myopia, but few such interactions have been identified. Here, we aimed to identify genetic variants that interact with education level to confer susceptibility to myopia. Two groups of unrelated participants of European ancestry from UK Biobank were studied. A ‘Stage-I’ sample of 88,334 participants whose refractive error (avMSE) was measured by autorefraction and a ‘Stage-II’ sample of 252,838 participants who self-reported their age-of-onset of spectacle wear (AOSW) but who did not undergo autorefraction. Genetic variants were prioritized via a 2-step screening process in the Stage-I sample: Step 1 was a genome-wide association study for avMSE; Step 2 was a variance heterogeneity analysis for avMSE. Genotype-by-education interaction tests were performed in the Stage-II sample, with University education coded as a binary exposure. On average, participants were 58 years-old and left full-time education when they were 18 years-old; 35% reported University level education. The 2-step screening strategy in the Stage-I sample prioritized 25 genetic variants (GWAS P