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Education and myopia: assessing the direction of causality by mendelian randomisation

BMJ 2018; 361 doi: https://doi.org/10.1136/bmj.k2022 (Published 06 June 2018) Cite this as: BMJ 2018;361:k2022

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Intense schooling linked to myopia

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Education and myopia: assessing the direction of causality by mendelian randomisation

  1. Edward Mountjoy, postgraduate researcher1 2,
  2. Neil M Davies, research fellow1 2,
  3. Denis Plotnikov, postgraduate researcher3,
  4. George Davey Smith, professor1 2,
  5. Santiago Rodriguez, senior lecturer1 2,
  6. Cathy E Williams, reader2,
  7. Jeremy A Guggenheim, professor3,
  8. Denize Atan, consultant senior lecturer4
  1. 1MRC Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol, UK
  2. 2Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
  3. 3School of Optometry and Vision Sciences, Cardiff University, Cardiff, UK
  4. 4Translational Health Sciences, Bristol Medical School, University of Bristol, Biomedical Sciences Building, Bristol BS8 1TD, UK
  1. Correspondence to: D Atan Denize.Atan{at}bristol.ac.uk
  • Accepted 19 April 2018

Abstract

Objectives To determine whether more years spent in education is a causal risk factor for myopia, or whether myopia is a causal risk factor for more years in education.

Design Bidirectional, two sample mendelian randomisation study.

Setting Publically available genetic data from two consortiums applied to a large, independent population cohort. Genetic variants used as proxies for myopia and years of education were derived from two large genome wide association studies: 23andMe and Social Science Genetic Association Consortium (SSGAC), respectively.

Participants 67 798 men and women from England, Scotland, and Wales in the UK Biobank cohort with available information for years of completed education and refractive error.

Main outcome measures Mendelian randomisation analyses were performed in two directions: the first exposure was the genetic predisposition to myopia, measured with 44 genetic variants strongly associated with myopia in 23andMe, and the outcome was years in education; and the second exposure was the genetic predisposition to higher levels of education, measured with 69 genetic variants from SSGAC, and the outcome was refractive error.

Results Conventional regression analyses of the observational data suggested that every additional year of education was associated with a more myopic refractive error of −0.18 dioptres/y (95% confidence interval −0.19 to −0.17; P<2e-16). Mendelian randomisation analyses suggested the true causal effect was even stronger: −0.27 dioptres/y (−0.37 to −0.17; P=4e-8). By contrast, there was little evidence to suggest myopia affected education (years in education per dioptre of refractive error −0.008 y/dioptre, 95% confidence interval −0.041 to 0.025, P=0.6). Thus, the cumulative effect of more years in education on refractive error means that a university graduate from the United Kingdom with 17 years of education would, on average, be at least −1 dioptre more myopic than someone who left school at age 16 (with 12 years of education). Myopia of this magnitude would be sufficient to necessitate the use of glasses for driving. Sensitivity analyses showed minimal evidence for genetic confounding that could have biased the causal effect estimates.

Conclusions This study shows that exposure to more years in education contributes to the rising prevalence of myopia. Increasing the length of time spent in education may inadvertently increase the prevalence of myopia and potential future visual disability.

Footnotes

  • Contributors: DA and JAG conceived the study. EM, DP, and NMD cleaned and analysed the data with input from GDS. EM wrote the first draft of the manuscript with DA and JAG. DA and JAG revised the draft. All authors contributed to data interpretation, critical revisions, and final approval of the manuscript. DA is the guarantor.

  • Funding: EM is funded by the Medical Research Council (MRC) and Bristol Centre for Systems Biomedicine; DP by the global education programme of the Russian Federation government; JAG and CW by the National Eye Research Centre (grant SAC015) and CEW by the National Institute for Health Research (senior research fellowship SRF-2015-08-005); NMD by the Economics and Social Research Council (future research leaders grant ES/N000757/1). GDS works in the MRC Integrative Epidemiology Unit at the University of Bristol (MC_UU_12013/1, MC_UU_12013/8, MC_UU_12013/9). The funders had no role in the study design, data collection, analysis, interpretation, or writing, nor in the decision to submit the article for publication.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years ; no other relationships or activities that could appear to have influenced the submitted work .

  • Ethical approval: The UK Biobank Resource and Access Committee approved this research (application #8786). Anonymised phenotype and genetic data are available from UK Biobank on application.

  • Data sharing: Participants consented to data sharing as described in the population cohorts and are not identifiable in these analyses. Code implementing the statistical methods to analyse the data are available from https://github.com/edm1/myopia-education-MR.

  • Transparency: The corresponding author (DA) is guarantor of the paper and affirms that the manuscript is an honest, accurate and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned have been explained.

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/.

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