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

G. Cuellar-Partida, Y. Lu, P.F. Kho, A.W. Hewitt, H.E. Wichmann, S. Yazar, D. Stambolian, J.E. Bailey-Wilson, R. Wojciechowski, J.J. Wang, P. Mitchell, David Mackey, S. Macgregor

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Abstract

© 2016 Wiley Periodicals, Inc. 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.
Original languageEnglish
Pages (from-to)66-72
JournalGenetic Epidemiology
Volume40
Issue number1
DOIs
Publication statusPublished - 2016

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Myopia
Genetic Predisposition to Disease
Random Allocation
Education
Observational Studies
Refractive Errors
Mendelian Randomization Analysis
Social Sciences
Genome-Wide Association Study
Vision Disorders
Least-Squares Analysis
Causality
Meta-Analysis
Public Health
Population

Cite this

Cuellar-Partida, G. ; Lu, Y. ; Kho, P.F. ; Hewitt, A.W. ; Wichmann, H.E. ; Yazar, S. ; Stambolian, D. ; Bailey-Wilson, J.E. ; Wojciechowski, R. ; Wang, J.J. ; Mitchell, P. ; Mackey, David ; Macgregor, S. / Assessing the Genetic Predisposition of Education on Myopia: A Mendelian Randomization Study. In: Genetic Epidemiology. 2016 ; Vol. 40, No. 1. pp. 66-72.
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Cuellar-Partida, G, Lu, Y, Kho, PF, Hewitt, AW, Wichmann, HE, Yazar, S, Stambolian, D, Bailey-Wilson, JE, Wojciechowski, R, Wang, JJ, Mitchell, P, Mackey, D & Macgregor, S 2016, 'Assessing the Genetic Predisposition of Education on Myopia: A Mendelian Randomization Study' Genetic Epidemiology, vol. 40, no. 1, pp. 66-72. https://doi.org/10.1002/gepi.21936

Assessing the Genetic Predisposition of Education on Myopia: A Mendelian Randomization Study. / Cuellar-Partida, G.; Lu, Y.; Kho, P.F.; Hewitt, A.W.; Wichmann, H.E.; Yazar, S.; Stambolian, D.; Bailey-Wilson, J.E.; Wojciechowski, R.; Wang, J.J.; Mitchell, P.; Mackey, David; Macgregor, S.

In: Genetic Epidemiology, Vol. 40, No. 1, 2016, p. 66-72.

Research output: Contribution to journalArticle

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AU - Lu, Y.

AU - Kho, P.F.

AU - Hewitt, A.W.

AU - Wichmann, H.E.

AU - Yazar, S.

AU - Stambolian, D.

AU - Bailey-Wilson, J.E.

AU - Wojciechowski, R.

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AU - Mitchell, P.

AU - Mackey, David

AU - Macgregor, S.

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AB - © 2016 Wiley Periodicals, Inc. 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.

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