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Interaction Between Lifestyle and Genetic Susceptibility in Myopia: the Generation R Study


Enthoven CA, Tideman JWL, Polling JR, Tedja MS, Raat H, Iglesias AI, Verhoeven VJM, Klaver CCW





European Journal of Epidemiology


  • Myopia is a refractive error of the eye caused by a complex interplay between nature and nurture.

  • The aim of this study was to investigate whether environmental risk factors can influence the genetic effect in children developing myopia. A total of 3422 children participating in the birth-cohort study Generation R underwent an extensive eye examination at 9 years with measurements of refractive error and axial length corneal radius ratio (AL/CR).

  • Environmental risk factors were evaluated using a questionnaire, and environmental risk scores (ERS) were calculated using backward regression analyses.

  • Genetic risk scores (GRS) were calculated based on all currently known risk variants for myopia.

  • Gene-environment interaction (G×E) was investigated using linear and logistic regression analyses. The predictive value of G×E and parental myopia was estimated using receiver operating characteristic curves.

  • Myopia prevalence was 12%. Both GRS (P < 0.01) and ERS (P < 0.01) were significantly associated with myopia and AL/CR, as was G×E interaction (P < 0.01 for myopia; P = 0.07 for AL/CR). The predictive value of parental myopia was 0.67 (95% CI 0.65-0.70), similar to the values of GRS (0.67; 95% CI 0.64-0.70; P = 0.98) and ERS (0.69; 95% CI 0.66-0.72; P = 0.98). Adding G×E interaction significantly improved the predictive value to 0.73 (95% CI 0.70-0.75; P < 0.01).

  • This study provides evidence that nature and nurture are equally important for myopia and AL/CR; however, the combination has the strongest influence.

  • Since myopia genes are common in the population, adjustment of lifestyle should be a major focus in the prevention of myopia.