Assessing the Genetic Predisposition of Education on Myopia: A Mendelian Randomization Study

Abstract

Myopia is the largest cause of uncorrected visual impairments globally and its recent dramatic increase in the population has made it a major public health problem. In observational studies, educational attainment has been consistently reported to be correlated to myopia. Nonetheless, correlation does not imply causation. Observational studies do not tell us if education causes myopia or if instead there are confounding factors underlying the association. In this work, we use a two-step least squares instrumental-variable (IV) approach to estimate the causal effect of education on refractive error, specifically myopia. We used the results from the educational attainment GWAS from the Social Science Genetic Association Consortium to define a polygenic risk score (PGRS) in three cohorts of late middle age and elderly Caucasian individuals (N=5,649). In a meta-analysis of the three cohorts, using the PGRS as an IV, we estimated that each z-score increase in education (approximately 2 years of education) results in a reduction of 0.92 ± 0.29 diopters (P=1.04×10−3). Our estimate of the effect of education on myopia was higher (P=0.01) than the observed estimate (0.25 ± 0.03 diopters reduction per education z-score [~2 years] increase). This suggests that observational studies may actually underestimate the true effect. Our Mendelian Randomization (MR) analysis provides new evidence for a causal role of educational attainment on refractive error.

Phenotypic and genotypic correlation between myopia and intelligence

“…However, the possibility of a number of genes of small effect, perhaps inherited simultaneously and linked, that control neural signaling influencing ocular growth and learning abilities remains interesting. Recent research has identified gene-environment interactions between educational attainment and myopia48, whilst PRS for educational attainment predict refractive error and when incorporated as an instrumental variable in Mendelian randomization (MR) analysis support the notion that educational attainment is causally related to refractive error49. The education PRS in the MR study only explained 0.25% of refractive error variance, comparatively less than the variance explained by IQ in our analysis.…”

Prevalence of refractive errors in Colombia: MIOPUR study

“…In our study, a higher prevalence of myopia was found in the population with a secondary or higher level of education, although in the multivariate analysis this association was not statistically significant (OR 1.14, 95% CI 0.86 to 1.52). Recently, Cuellar-Partida et al used a Mendelian randomisation approach and suggested that observational studies, such as the one we conducted, could underestimate the true effect of educational level on the prevalence of myopia in populations 21. In the case of hyperopia, in our study, the highest educational level was shown as protective (OR 0.59, 95% CI 0.47 to 0.74).…”

Serum 25-hydroxyvitamin D level is associated with myopia in the Korea national health and nutrition examination survey

“…[66] In the former study, low serum 25(OH)D levels were significantly associated with myopia, especially high myopia in adolescents in Korea. [36] The population in the previous study was in their growth period and myopia was progressing; most studies seeking the cause of myopia are targeted at this age group, [3,10,15,18,40,47] whereas the present study targeted a large adult population in which ocular growth was complete. In this regard, 25(OH)D and sun exposure levels may have different mechanisms in the prevalence of myopia and exert independent effects on myopia.…”

“…[7–9] Although the cause of myopia is as yet unclear, genetic and environmental factors may contribute to its development. [10–15] Some recent studies suggested that increasing time spent outdoors may prevent the development of myopia, [14–17] although the results of some epidemiological studies oppose this theory. [18,19] …”