June 1, 2021
By Senuri Karunaratne BSc, OD, Mel.; Research Optometrist, Brien Holden Vision Institute
Myopia is thought to result from a combination of an individual’s environment and genetic makeup. Knowledge of an individual’s susceptibility, for example, with parental myopia or genetic risk score may help manage children at risk. In this study, Enthoven et al. investigated the relation between parental myopia, genetics, and environmental risk factors for their predictive value in identifying children at risk of developing myopia.
The study included 3,422 participants from the Generation R birth cohort who attended the research center in the Netherlands at the age of 9 for an eye examination. Cycloplegic autorefraction was conducted in 42% of the sample, whereas axial length and corneal radius were measured, and AL/CR was determined in all participants. Spherical equivalent refraction of -0.50D or worse in at least one eye was categorized as a myope. Parents completed questionnaires addressing outdoor exposure, indoor activities, near activities, and parental myopia to evaluate environmental risk scores (ERS). Genotyping was performed, and genetic risk scores (GRS) were determined. The predictive value of myopia versus no myopia was calculated for parental myopia, ERS, GRS, and the combination.
Myopia prevalence in the Generation R cohort was 12%. The environmental risk profile in this study for myopia reflected previous findings, with increased reading time (>1 book/week), reduced reading distance, and reduced time outdoors (<7 hrs/week). ERS had a significant association to AL/CR with a variance of 1.1% and a variance of 2.1% for myopia. Genetic risk scores were significantly correlated to AL/CR (4.4%) and myopia (2.3%). In considering ERS and GRS, parental myopia (one or more parents) was a common factor. Individually the predictive value of myopia for ERS, GRS, and parental myopia was 0.69, 0.67, and 0.67, respectively, suggesting that parental myopia could be an equally predictive risk factor to ERS and GRS. Additionally, when combined (ERS + GRS + parental myopia), the predictive value of myopia increased to 0.73 and showed a strong association to myopia and a borderline association to AL/CR.
This study had the advantage of a large dataset, access to genetic screening, and the use of lifestyle questionnaires by a large population of parents. Despite this, a key limitation was the self-reported ERS and the cross-sectional study design. This study determined the predictive values of myopia, which were all comparable. The association between GRS and ERS was significant; it was suggested that lifestyle might be partly genetically determined. Parental myopia represented both genetic and environmental risk factors. Since genetic testing may not be feasible in young children, ascertaining parental myopia and ERS was suggested as applicable to detect children at risk. These findings can help identify increased myopia risk in children and guide lifestyle modifications without the reliance on complex genetic testing.
Interaction Between Lifestyle and Genetic Susceptibility in Myopia: The Generation R Study
Clair A. Enthoven, Jan Willem Lodewijk Tideman, Jan Roelof Polling, Milly S. Tedja, Hein Raat, Adriana I. Iglesias, Virginie J. M. Verhoeven, Caroline C. W. Klaver
Purpose: The aim of this study was to investigate whether environmental risk factors can influence the genetic effect in children developing myopia.
Method: 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.
Results: 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).
Conclusion: 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.
Enthoven, C. A., Tideman, J. W. L., Polling, J. R., Tedja, M. S., Raat, H., Iglesias, A. I., … & Klaver, C. C. (2019). Interaction between lifestyle and genetic susceptibility in myopia: the Generation R study. European journal of epidemiology, 34(8), 777-784.
Senuri Karunaratne graduated from the University of Melbourne with a Doctorate in Optometry. Following her experience in clinical practice, she transitioned into her role as a research optometrist at BHVI. She is interested in myopia progression and myopia control devices.