Assessing the Genetic Predisposition of Education on Myopia: A Mendelian Randomization Study.
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.
Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Gabriel
G
Cuellar-Partida
Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Yi
Y
Lu
Department of Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Pik Fang
PF
Kho
School of Medicine, Menzies Research Institute Tasmania, University of Tasmania, Hobart, Australia.
Alex W
AW
Hewitt
Helmholtz Centre Munich, Institute of Epidemiology I, Neuherberg, Germany.|Institute of Medical Statistics and Epidemiology, Technical University Munich, Germany.
H-Erich
HE
Wichmann
Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Australia.
Seyhan
S
Yazar
Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Dwight
D
Stambolian
Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Baltimore, Maryland, United States of America.
Joan E
JE
Bailey-Wilson
Wilmer Eye Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Robert
R
Wojciechowski
Centre for Vision Research, Westmead Millennium Institute of Medical Research and Department of Ophthalmology, University of Sydney, Sydney, Australia.
Jie Jin
JJ
Wang
Centre for Vision Research, Westmead Millennium Institute of Medical Research and Department of Ophthalmology, University of Sydney, Sydney, Australia.
Paul
P
Mitchell
Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Australia.
David A
DA
Mackey
Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Stuart
S
MacGregor
D000368:Aged; D001315:Australia; D004522:Educational Status; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D006801:Humans; D016018:Least-Squares Analysis; D008297:Male; D057182:Mendelian Randomization Analysis; D008875:Middle Aged; D009216:Myopia / Q000209:etiology* / Q000235:genetics; D044465:White People / Q000235:genetics
Mendelian randomization; education; instrumental variable; myopia; polygenic risk scores; refractive error