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Assessing the Genetic Predisposition of Education on Myopia: A Mendelian Randomization Study
Author(s) -
CuellarPartida Gabriel,
Lu Yi,
Kho Pik Fang,
Hewitt Alex W.,
Wichmann H.Erich,
Yazar Seyhan,
Stambolian Dwight,
BaileyWilson Joan E.,
Wojciechowski Robert,
Wang Jie Jin,
Mitchell Paul,
Mackey David A.,
MacGregor Stuart
Publication year - 2016
Publication title -
genetic epidemiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.301
H-Index - 98
eISSN - 1098-2272
pISSN - 0741-0395
DOI - 10.1002/gepi.21936
Subject(s) - mendelian randomization , observational study , confounding , refractive error , educational attainment , genetic association , instrumental variable , demography , causal inference , dioptre , medicine , population , ophthalmology , genetics , visual acuity , biology , statistics , environmental health , single nucleotide polymorphism , genotype , genetic variants , mathematics , pathology , sociology , gene , economics , economic growth
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.