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Cited by 299Ophthalmology and Visual Impairment StudiesGenetic Associations and EpidemiologyGenetics and Physical Performance

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

Open access
Mountjoy, Edward, Davies, Neil M, Plotnikov, Denis, Smith, George Davey, Rodriguez, Santiago, Williams, Cathy E, Guggenheim, Jeremy A, Atan, Denize·2018·BMJ
DOI 10.1136/bmj.k2022PMC PMC5987847

Published version of a preprint

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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.

AI snapshot

Written from the paper’s full text.

TL;DR

Bidirectional mendelian randomisation in UK Biobank found that more years of education causally increases myopia, whereas myopia does not appear to cause more years of education. The causal effect of education on refractive error was larger than the observational association.

Key findings

  • Observational regression showed each additional year of education was associated with a more myopic refractive error of −0.18 dioptres/y (95% CI −0.19 to −0.17; P<2e-16).
  • Mendelian randomisation estimated a stronger causal effect: −0.27 dioptres/y per additional year of education (95% CI −0.37 to −0.17; P=4e-8).
  • In the reverse direction, there was little evidence that myopia affected years in education: −0.008 y/dioptre (95% CI −0.041 to 0.025; P=0.6).
  • The cumulative effect meant a UK university graduate with 17 years of education would be at least −1 dioptre more myopic than someone who left school at age 16 with 12 years of education; sensitivity analyses showed minimal evidence for genetic confounding.

Methods

  • Bidirectional, two-sample mendelian randomisation using 67,798 men and women from England, Scotland, and Wales in UK Biobank with valid education, refractive error, and genetic data.
  • Genetic instruments were 44 variants associated with myopia from 23andMe and 69 variants associated with educational attainment from the Social Science Genetic Association Consortium; analyses used weighted allele scores and two-stage least squares with age and sex as covariates.
  • Sensitivity analyses included confounding bias plots, MR-Egger, weighted median/mode methods, alternative education coding, exclusion of university/college attendees, and Durbin-Wu-Hausman tests.

Limitations

  • The paper states that UK Biobank participants are more highly educated and healthier than the general UK population, so selection bias could affect both observational and mendelian randomisation estimates.
  • The paper reports some evidence of confounding by northing and principal component 9, and states that horizontal pleiotropy cannot be ruled out unequivocally, although sensitivity analyses suggested little evidence of directional pleiotropy.
  • The paper notes that mendelian randomisation cannot determine which specific components of educational practices caused increased myopia; the text also makes evident that refractive error was cross-sectionally measured by non-cycloplegic autorefraction, myopia in the 23andMe GWAS was self-reported, and education was harmonised with assumptions such as assigning 21 years to university graduates.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1136/bmj.k2022

Cites

81 of 81 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 45 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    There was little evidence that refractive error affected time spent in education (βIV=−0.008 y/dioptre, 95% confidence interval −0.041 to 0.025, P=0.6).

    “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).”
    • Also stated in: § Mendelian randomisation analyses: more time spent in education causes myopia · hedged
      “Conversely, using the myopia allele score as the instrumental variable in mendelian randomisation analyses provided little evidence that refractive error affected time spent in education (βIV=−0.008 y/dioptre, 95% confidence interval −0.041 to 0.025, P=0.6) (table 2; fig 3).”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: The genetic instrumental variables are not associated with any confounders of the exposure-outcome relation.
    • The authors state this as an assumption: The genetic instrumental variables are only associated with the outcome through the exposure.
    • The authors state this as an assumption: Genetic variants with pleiotropic effects are invalid instrumental variables.
  • Findingown data

    The relation between time in education and refractive error was linear for those leaving full time education between ages 15 and 18, with every additional year associated with a higher myopic refractive error by −0.25 dioptres/y.

    “The relation was linear for those leaving full time education between the ages of 15 and 18 years, meaning that every additional year in education was associated with a higher myopic refractive error by −0.25 dioptres/y.”
    Quote in the paperNot a substantial claim
  • Findingown data

    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) in UK Biobank participants.

    “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).”
    • Also stated in: § Observational analyses: higher levels of education are associated with myopia · plain
      “On average, every additional year spent in 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).”
    Quote in the paperSubstantial claim
  • Findingown data

    For those leaving full time education after age 18 years, the rate of myopic refractive error change slowed to −0.10 dioptres/y.

    “For those leaving full time education after age 18 years, the rate slowed to −0.10 dioptres/y (fig 2).”
    Quote in the paperNot a substantial claim
  • Findingown data

    Easting was weakly associated with the myopia allele score (P=0.01).

    “It was weakly associated with the myopia allele score (P=0.01).”
    Quote in the paperNot a substantial claim
  • May combine two claims. 30
  • Classified as probably not a substantial claim. 13

  • May combine two claims.

    Findingown data

    Northing was negatively associated with time spent in education (β=−1.6e-6, 95% confidence interval −1.8e-6 to −1.5e-6) and positively with refractive error (β=1.2e-6, 9.8e-7 to 1.3e-6).

    “there was evidence that the geographical coordinate, northing (measured northward distance in UK) was negatively associated with time spent in education (β=−1.6e-6, 95% confidence interval −1.8e-6 to −1.5e-6) and positively with refractive error (β=1.2e-6, 9.8e-7 to 1.3e-6).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    Easting was positively associated with time spent in education (β=8.9e-7, 95% confidence interval 6.8e-7 to 1.1e-6) and negatively associated with refractive error (β=−1.0e-6, −1.3e-6 to −8.1e-6).

    “In contrast, the geographical easting coordinate was positively associated with time spent in education (β=8.9e-7, 95% confidence interval 6.8e-7 to 1.1e-6) and negatively associated with refractive error (β=−1.0e-6, −1.3e-6 to −8.1e-6).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    PC9 was associated with a self reported place of birth in Wales and with a −0.17 dioptre (95% confidence interval −0.05 to −0.28) more myopic refractive error, on average (P=4e-3) compared with those who reported being born in England.

    “Additional analyses showed that PC9 was associated with a self reported place of birth in Wales (see supplementary figure S2) and also with a −0.17 dioptre (95% confidence interval −0.05 to −0.28) more myopic refractive error, on average (P=4e-3) compared with those who reported being born in England.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Northing was associated with the time spent in education (P=7e-5) and myopia (P=6e-3) allele scores.

    “Northing was also associated with the time spent in education (P=7e-5) and myopia (P=6e-3) allele scores (see supplementary table 2).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Using the Durbin-Wu-Hausman test, there was weak evidence that the instrumental variable estimate using the time spent in education allele score differed from the observational point estimate (P=0.06), with the instrumental variable estimate suggesting a larger negative association.

    “Using the Durbin-Wu-Hausman test for endogeneity, we found weak evidence that the instrumental variable estimate using the time spent in education allele score differed from the observational point estimate (Durbin-Wu-Hausman P=0.06), with the instrumental variable estimate suggesting a larger negative association (table 2).”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The genetic variants used as instrumental variables affect refractive error only through their effect on education (no horizontal pleiotropy).
    • Rests on an assumption: The genetic variants used as instrumental variables are not associated with confounders of the education–myopia relation (independence assumption).

  • May combine two claims.

    Findingown data

    Sensitivity analyses (mendelian randomisation-Egger and mode based mendelian randomisation) suggested little evidence of unbalanced horizontal pleiotropy in the relation between education and myopia, although such bias cannot be ruled out unequivocally.

    “Sensitivity analyses (mendelian randomisation-Egger and mode based mendelian randomisation; see supplementary table S3) suggested little evidence of unbalanced horizontal pleiotropy in the relation between education and myopia, although such bias cannot be ruled out unequivocally.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The confounding bias plot suggested that inclusion of the northing variable in the instrumental variable analysis would result in a greater degree of bias for the education allele score but not for the myopia allele score.

    “Compared with standard regression, the confounding bias plot suggested that inclusion of the northing variable in the instrumental variable analysis would result in a greater degree of bias for the education allele score but not for the myopia allele score (fig 4).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Genetic variants are not modifiable and are largely free from confounding.

    “since genetic variants are not modifiable and are largely free from confounding.32 33”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites 32 33

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    Genetics cannot explain the rapid increase in the prevalence of myopia over one or two generations.

    “however, genetics cannot explain the rapid increase in the prevalence of myopia over one or two generations.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    With a sample size of n=69 798, there was 80% power to detect an effect of time spent in education on refractive error ≥0.14 dioptres/y, and 80% power to detect an effect ≥0.048 y/dioptre in the reciprocal direction, suggesting that this study had sufficient power to detect an effect of myopia on education, if present.

    “With a sample size of n=69 798, there was 80% power to detect an effect of time spent in education on refractive error ≥0.14 dioptres/y. In the reciprocal direction, there was 80% power to detect an effect ≥0.048 y/dioptre (see supplementary figure 1), suggesting that this study had sufficient power to detect an effect of myopia on education, if present.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    The results of a mendelian randomisation sensitivity analysis restricted to participants born in England were essentially unchanged, providing evidence that imprecision in quantifying years spent in education due to differences in school leaving age did not adversely affect the results.

    “However, the results of a mendelian randomisation sensitivity analysis restricted to participants born in England were essentially unchanged (see supplementary table 4), providing evidence that imprecision in quantifying years spent in education due to differences in school leaving age did not adversely affect the results.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationreasoning

    Myopia of this magnitude would be sufficient to necessitate the use of glasses for driving.

    “Myopia of this magnitude would be sufficient to necessitate the use of glasses for driving.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Increasing the length of time spent in education may inadvertently increase the prevalence of myopia and potential future visual disability.

    “Increasing the length of time spent in education may inadvertently increase the prevalence of myopia and potential future visual disability.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    All mendelian randomisation methods (mendelian randomisation-Egger, weighted mode, and weighted median) yielded similar causal estimates in magnitude and direction, such that increasing time spent in education led to a more myopic refractive error (by −0.17 to −0.40 dioptres/y), whereas there was little evidence that a more myopic refractive error led to more time spent in education.

    “However, all methods yielded similar causal estimates in magnitude and direction, such that increasing time spent in education led to a more myopic refractive error (by −0.17 to −0.40 dioptres/y), whereas there was little evidence that a more myopic refractive error led to more time spent in education (see supplementary table 3).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    The myopia allele score explained 4.32% (F=3155) of the variance in average mean spherical equivalent refractive error of participants in UK Biobank, and the education allele score explained 0.71% (F=464) of the variance in time spent in education.

    “The myopia allele score explained 4.32% (F=3155) of the variance in average mean spherical equivalent refractive error of participants in UK Biobank and the education allele score explained 0.71% (F=464) of the variance in time spent in education.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    The mendelian randomisation effect estimate was even greater in magnitude than the observational estimate (−0.27 v −0.18 dioptres), suggesting that unmeasured confounders may have attenuated the latter relation.

    “The mendelian randomisation effect estimate was even greater in magnitude than the observational estimate (−0.27 v −0.18 dioptres) suggesting that unmeasured confounders may have attenuated the latter relation.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Both myopia and educational attainment have a heritable component.

    “Both myopia and educational attainment have a heritable component14 15 16 17 18 19 20”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites 14 15 16 17 18 19 20

      Not checked in the free run.

  • May combine two claims.

    Study design and conductown data

    There was little evidence that the mendelian randomisation-Egger intercept deviated from zero either for more time in education causing refractive error (intercept=0.007, SE=0.006, P=0.2) or refractive error causing more time in education (intercept=−0.002, SE=0.007, P=0.8), indicating that there was little evidence for directional genetic pleiotropy.

    “In practice, there was little evidence that the Egger intercept deviated from zero either for more time in education causing refractive error (intercept=0.007, SE=0.006, P=0.2) or refractive error causing more time in education (intercept=−0.002, SE=0.007, P=0.8), indicating that there was little evidence for directional genetic pleiotropy.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Randomised controlled trials have shown convincingly that time spent outdoors in childhood partially protects against the development of myopia.

    “Randomised controlled trials have shown convincingly that time spent outdoors in childhood partially protects against the development of myopia,24 25”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites 24 25

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The progression of myopia is faster in winter months, thus supporting the hypothesis that exposure to natural light is important.

    “The progression of myopia is faster in winter months, thus supporting the hypothesis that exposure to natural light is important.78 79”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [78] Cui D Trier K Munk Ribel-Madsen S Effect of day length on eye growth, myopia progression, and change of corneal power in myopic children. Ophthalmology 2013; 120: 1074- 9. 10.1016/j.ophtha.2012.10.022. 23380471

      Not checked in the free run.

    • cites [79] Gwiazda J Deng L Manny R Norton TT COMET Study Group Seasonal variations in the progression of myopia in children enrolled in the correction of myopia evaluation trial. Invest Ophthalmol Vis Sci 2014; 55: 752- 8. 10.1167/iovs.13-13029. 24408976 PMC3915767

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    There are other well established associations between myopia and urbanisation, reduced light exposure, socioeconomic position, near work, and prenatal factors, and several of these factors either confound the relation between education and myopia or may work synergistically to exacerbate the effect.

    “There are other well established associations between myopia and urbanisation, reduced light exposure, socioeconomic position, near work, and prenatal factors,21 65 66 67 and several of these factors either confound the relation between education and myopia or may work synergistically to exacerbate the effect—for example, in countries where myopia prevalence is particularly high.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [21] Morgan IG French AN Ashby RS The epidemics of myopia: Aetiology and prevention. Prog Retin Eye Res 2018; 62: 134- 49. 10.1016/j.preteyeres.2017.09.004. 28951126

      Not checked in the free run.

    • cites [65] Williams KM Bentham GC Young IS Association Between Myopia, Ultraviolet B Radiation Exposure, Serum Vitamin D Concentrations, and Genetic Polymorphisms in Vitamin D Metabolic Pathways in a Multicountry European Study. JAMA Ophthalmol 2016; 135: 47- 53. 10.1001/jamaophthalmol.2016.4752. 27918775

      Not checked in the free run.

    • cites [66] Hua W-J Jin J-X Wu X-Y Elevated light levels in schools have a protective effect on myopia. Ophthalmic Physiol Opt 2015; 35: 252- 62. 10.1111/opo.12207. 25913873

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    Without knowing the function of the genetic variants and how they influence the traits described, it is possible that some single nucleotide polymorphisms may influence the outcome through a pathway that does not involve the exposure-that is, through horizontal pleiotropy.

    “Yet, without knowing the function of the genetic variants and how they influence the traits described here, it is possible that some single nucleotide polymorphisms may influence the outcome through a pathway that does not involve the exposure—that is, through horizontal pleiotropy.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Higher light exposure is correlated with lower myopia risk, and it is possible that those who spend more years in education have less exposure to natural light.

    “Others have correlated higher light exposure with lower myopia risk,66 77 and it is possible that those who spend more years in education have less exposure to natural light.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [66] Hua W-J Jin J-X Wu X-Y Elevated light levels in schools have a protective effect on myopia. Ophthalmic Physiol Opt 2015; 35: 252- 62. 10.1111/opo.12207. 25913873

      Not checked in the free run.

    • cites [77] Williams KM Bentham GC Young IS Association Between Myopia, Ultraviolet B Radiation Exposure, Serum Vitamin D Concentrations, and Genetic Polymorphisms in Vitamin D Metabolic Pathways in a Multicountry European Study. JAMA Ophthalmol 2017; 135: 47- 53. 10.1001/jamaophthalmol.2016.4752. 27918775

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    There are countries with poorly developed education systems in which the prevalence of myopia is low, and hence any causal relation between intelligence and myopia is unlikely.

    “Moreover, there are countries with poorly developed education systems in which the prevalence of myopia is low,61 62 63 64 and hence any causal relation between intelligence and myopia is unlikely.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [61] Gao Z Meng N Muecke J Refractive error in school children in an urban and rural setting in Cambodia. Ophthalmic Epidemiol 2012; 19: 16- 22. 10.3109/09286586.2011.632703 22273355

      Not checked in the free run.

    • cites [62] Garner LF Kinnear RF Klinger JD McKellar MJ Prevalence of myopia in school children in Vanuatu. Acta Ophthalmol (Copenh) 1985; 63: 323- 6. 10.1111/j.1755-3768.1985.tb06814.x. 3875961

      Not checked in the free run.

    • cites [63] Garner LF Owens H Kinnear RF Frith MJ Prevalence of myopia in Sherpa and Tibetan children in Nepal. Optom Vis Sci 1999; 76: 282- 5. 10.1097/00006324-199905000-00014 10375242

      Not checked in the free run.

  • May combine two claims.

    Study design and conductown data

    There was some evidence of confounding by the variables northing and PC9, of which the latter identified people from Wales.

    “There was some evidence of confounding by the variables northing and PC9, of which the latter identified people from Wales.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationnone given

    A difference of −1 dioptre would blur vision on a Snellen visual acuity chart to 6/18 and affect the ability to drive without glasses.

    “A difference of this magnitude would blur vision on a Snellen visual acuity chart to 6/18 and affect the ability to drive without glasses.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    The Cuellar-Partida et al study was under-powered and the authors did not investigate the possibility of horizontal genetic pleiotropy or reverse causation.

    “However, the study was under-powered and the authors did not investigate the possibility of horizontal genetic pleiotropy or reverse causation.68”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [68] Cuellar-Partida G Lu Y Kho PF Assessing the Genetic Predisposition of Education on Myopia: A Mendelian Randomization Study. Genet Epidemiol 2016; 40: 66- 72. 10.1002/gepi.21936. 26497973 PMC4915592

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    Given the ubiquity of exposure to education in populations with available genotype data, it is not possible to assess those who were completely free of the outcome, specifically education.

    “Given the ubiquity of exposure to education in populations with available genotype data, it is not possible to assess those who were completely free of the outcome, specifically education.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable).

    Premisecitation

    Mendelian randomisation is a particularly powerful approach for testing causal hypotheses in epidemiology.

    “Mendelian randomisation is a particularly powerful approach for testing causal hypotheses in epidemiology.56 57”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [56] Davey Smith G Ebrahim S What can mendelian randomisation tell us about modifiable behavioural and environmental exposures? BMJ 2005; 330: 1076- 9. 10.1136/bmj.330.7499.1076. 15879400 PMC557238

      Not checked in the free run.

    • cites [57] VanderWeele TJ Tchetgen Tchetgen EJ Cornelis M Kraft P Methodological challenges in mendelian randomization. Epidemiology 2014; 25: 427- 35. 10.1097/EDE.0000000000000081. 24681576 PMC3981897

      Not checked in the free run.

  • May combine two claims.

    Study design and conductown data

    Although there are differences between the education system in England and Wales compared with Scotland, the results held true when analyses were restricted to people from England.

    “Although there are some differences between the education system in England and Wales compared with Scotland, the results held true when analyses were restricted to people from England.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Axial eye growth occurs predominantly during the school years and levels of myopia tend to stabilise in adulthood, so any interventions to halt or prevent myopia need to be delivered in childhood.

    “Axial eye growth occurs predominantly during the school years81 and since levels of myopia tend to stabilise in adulthood23 any interventions to halt or prevent myopia need to be delivered in childhood.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [81] Wallman J Turkel J Trachtman J Extreme myopia produced by modest change in early visual experience. Science 1978; 201: 1249- 51. 10.1126/science.694514. 694514

      Not checked in the free run.

    • cites [23] Weale RA Epidemiology of refractive errors and presbyopia. Surv Ophthalmol 2003; 48: 515- 43. 10.1016/S0039-6257(03)00086-9 14499819

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    UK Biobank participants have been shown to be more highly educated, have healthier lifestyles, and have fewer self reported adverse health outcomes than expected compared with the general UK population.

    “UK Biobank participants have been shown to be more highly educated, have healthier lifestyles, and have fewer self reported adverse health outcomes than expected compared with the general UK population.58”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [58] Fry A Littlejohns TJ Sudlow C Comparison of Sociodemographic and Health-Related Characteristics of UK Biobank Participants With Those of the General Population. Am J Epidemiol 2017; 186: 1026- 34. 10.1093/aje/kwx246. 28641372 PMC5860371

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    The findings of this study have important implications for educational practices.

    “With the rapid increase in the global prevalence of myopia and the economic burden of myopia and its vision threatening complications, the findings of this study have important implications for educational practices.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationown data

    The larger standard errors in the university-excluded analysis were attributable in part to the reduced sample size (n=45,535).

    “This was attributable, in part, to the reduced sample size (n=45 535).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    The analyses in this study provided strong evidence that the relation arose from a causal effect of exposure to education on refractive error, and not through reverse causation or confounding by influences such as socioeconomic position.

    “Crucially, the analyses in this study provided strong evidence that the relation arose from a causal effect of exposure to education on refractive error, and not through reverse causation or confounding by influences such as socioeconomic position.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The genetic variants used as instrumental variables affect refractive error only through their effect on education (no horizontal pleiotropy).
    • Rests on an assumption: The genetic variants used as instrumental variables are not associated with confounders of the education–myopia relation (independence assumption).

  • May combine two claims.

    Premisecitation

    The current epidemic of myopia in developed East and South-East Asian countries over the past one or two generations seems to coincide with widening exposure to primary and secondary education, whereas educational outcomes are less clearly associated with myopia.

    “The current epidemic of myopia in developed East and South-East Asian countries over the past one or two generations seems to coincide with widening exposure to primary and secondary education, whereas educational outcomes (eg, in scientific, reading, and mathematical literacy) are less clearly associated with myopia, since many Western countries achieve top international rankings in student”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [60] Morgan IG Rose KA Myopia and international educational performance. Ophthalmic Physiol Opt 2013; 33: 329- 38. 10.1111/opo.12040. 23662964

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    The number of single nucleotide polymorphisms used in the previous study means it was more likely to include pleiotropic variants with direct effects both on exposure to education and on refractive error, and single nucleotide polymorphisms that are in linkage disequilibrium with refractive error variants.

    “The number of single nucleotide polymorphisms used in this previous study means it was more likely to include pleiotropic variants with direct effects both on exposure to education and on refractive error, and single nucleotide polymorphisms that are in linkage disequilibrium with refractive error variants.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Children with myopia tend to engage in less physical activity, such as sports, but physical activity in itself does not seem to be protective.

    “Children with myopia tend to engage in less physical activity, such as sports, but physical activity in itself does not seem to be protective.29 76”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [29] Guggenheim JA Northstone K McMahon G Time outdoors and physical activity as predictors of incident myopia in childhood: a prospective cohort study. Invest Ophthalmol Vis Sci 2012; 53: 2856- 65. 10.1167/iovs.11-9091. 22491403 PMC3367471

      Not checked in the free run.

    • cites [76] Deere K Williams C Leary S Myopia and later physical activity in adolescence: a prospective study. Br J Sports Med 2009; 43: 542- 4. 10.1136/bjsm.2008.049288. 19581405 PMC2913228

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    Policy makers should be aware that the educational practices used to educate children and to promote personal and economic health may have the unintended consequence of causing increasing levels of myopia and later visual disability.

    “Policy makers should be aware that the educational practices used to educate children and to promote personal and economic health may have the unintended consequence of causing increasing levels of myopia and later visual disability.”
    Quote in the paperNot a substantial claim
39 of 39

  • The authors state this as an assumption.

    The genetic instrumental variables are not associated with any confounders of the exposure-outcome relation.

    “Mendelian randomisation analyses are based on two pertinent assumptions: the genetic instrumental variables are not associated with any confounders of the exposure-outcome relation, and the genetic instrumental variables are only associated with the outcome through the exposure.”

  • The authors state this as an assumption.

    The genetic instrumental variables are only associated with the outcome through the exposure.

    “Mendelian randomisation analyses are based on two pertinent assumptions: the genetic instrumental variables are not associated with any confounders of the exposure-outcome relation, and the genetic instrumental variables are only associated with the outcome through the exposure.”

  • The authors state this as an assumption.

    Genetic variants with pleiotropic effects are invalid instrumental variables.

    “Under the second assumption of mendelian randomisation, genetic variants with pleiotropic effects are invalid instrumental variables.”

  • The paper relies on this without support.

    Mendelian randomisation reduces bias from confounding and reverse causation, to which observational epidemiology studies are susceptible.

    “This approach reduces bias from confounding and reverse causation, to which observational epidemiology studies are susceptible.”

  • The paper relies on this without support.

    Genotypes are randomly assigned at conception.

    “It exploits the fact that genotypes are randomly assigned at conception.”

  • The paper relies on this without support.

    The genetic variants used as instrumental variables affect refractive error only through their effect on education (no horizontal pleiotropy).

    “When using mendelian randomisation it is not necessary to know how the genetic variants used in the analysis cause the exposure. Yet, without knowing the function of the genetic variants and how they influence the traits described here, it is possible that some single nucleotide polymorphisms may influence the outcome through a pathway that does not involve the exposure—that is, through horizontal”

  • The paper relies on this without support.

    The genetic variants used as instrumental variables are not associated with confounders of the education–myopia relation (independence assumption).

    “Although more robust to confounding than standard observational studies, mendelian randomisation is not entirely immune. There was some evidence of confounding by the variables northing and PC9, of which the latter identified people from Wales.”
7 of 7

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • High-myopia count does not match the stated percentage

    Major

    Nine million is 0.18% of five billion, not almost 10%. The stated percentage would correspond to roughly 500 million people.

    Reported 10 · recomputed 0.18

  • Participant count differs between abstract and main text

    Minor

    The abstract reports 67 798 participants, whereas the methods, results, and tables report 69 798 for the analysis.

  • Easting estimate falls outside its reported confidence interval

    Minor

    The reported estimate of −1.0e-6 is outside the stated interval, whose endpoints are −1.3e-6 and −8.1e-6. The interval's endpoints are also in reverse numerical order.

3 of 3

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. [77]Williams KM Bentham GC Young IS Association Between Myopia, Ultraviolet B Radiation Exposure, Serum Vitamin D Concentrations, and Genetic Polymorphisms in Vitamin D Metabolic Pathways in a Multicountry European Study. JAMA Ophthalmol 2017; 135: 47- 53. 10.1001/jamaophthalmol.2016.4752. 27918775 · DOI

Cited by

Sorted by citations

Related

Authors
Mountjoy, E., Davies, N. M., Plotnikov, D., Smith, G. D., Rodriguez, S., Williams, C. E., Guggenheim, J. A., & Atan, D.
Affiliations
  • University of Bristol (GB)
  • Cardiff University (GB)
Corresponding author
Atan, Denize
ORCID
Venue
BMJ
Publisher
BMJ
Published
2018-06-06
Volume
361
Pages
k2022
ISSN
  • 1756-1833 (ISSN-L)
  • 0959-8138
DOI
10.1136/bmj.k2022
PMC
PMC5987847
OpenAlex
W2805662486
Semantic Scholar
bd731e114ec9814596212bddcb78a63eab36fce5
Cited by
299
References
81
Citations by year
2026: 16 · 2025: 48 · 2024: 41 · 2023: 42 · 2022: 44 · 2021: 45 · 2020: 23 · 2019: 33 · 2018: 5 · 2017: 1
FWCI
20.61
Type
journal article
Language
en
Update notices
correction (2018-07-04)
Open access
Licence
Locations
  • BMJ (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
  • HighWire Press Open Archive (submittedVersion)
  • Bristol Research (University of Bristol) (submittedVersion, cc-by)
  • Explore Bristol Research (submittedVersion, cc-by)
Funders
  • National Institute for Health and Care Research (SRF-2015-08-005)
  • Sight Research UK
  • Medical Research Council (MC_PC_17228, MC_UU_00011/1)
  • Economic and Social Research Council (ES/N000757/1)
Topics
  • Health Sciences › Medicine › Epidemiology › Ophthalmology and Visual Impairment Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Physical Performance
Keywords
myopia, years of schooling, refractive error, causal inference, bidirectional causality, genetic variants, educational attainment, genetic confounding, myopia prevalence, UK Biobank, 23andMe, sensitivity analysis
MeSH terms
Adult, Educational Status, Female, United Kingdom, Humans, Male, Myopia, Refractive Errors, Risk Factors, Prevalence, Mendelian Randomization Analysis

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-10.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-10.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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