Evidence That Emmetropization Buffers Against Both Genetic and Environmental Risk Factors for Myopia

Abstract

Citation: Pozarickij A, Enthoven CA, Ghorbani Mojarrad N, et al. Evidence that emmetropization buffers against both genetic and environmental risk factors for myopia. Invest Ophthalmol Vis Sci. 2020;61(2):41. https://doi.org/10.1167/iovs.61.2.41 PURPOSE.To test the hypothesis that emmetropization buffers against genetic and environmental risk factors for myopia by investigating whether risk factor effect sizes vary depending on children's position in the refractive error distribution. METHODS. Refractive error was assessed in participants from two birth cohorts: AvonLongitudinal Study of Parents and Children (ALSPAC) (noncycloplegic autorefraction) and Generation R (cycloplegic autorefraction). A genetic risk score for myopia was calculated from genotypes at 146 loci. Time spent reading, time outdoors, and parental myopia were ascertained from parent-completed questionnaires. Risk factors were coded as binary variables (0 = low, 1 = high risk). Associations between refractive error and each risk factor were estimated using either ordinary least squares (OLS) regression or quantile regression. RESULTS.Quantile regression: effects associated with all risk factors (genetic risk, parental myopia, high time spent reading, low time outdoors) were larger for children in the extremes of the refractive error distribution than for emmetropes and low ametropes in the center of the distribution. For example, the effect associated with having a myopic parent for children in quantile 0.05 vs. 0.50 was as follows: ALSPAC: age 15, -1.19 D (95% CI -1.75 to -0.63) vs. -0.13 D (-0.19 to -0.06), P = 0.001; Generation R: age 9, -1.31 D (-1.80 to -0.82) vs. -0.19 D (-0.26 to -0.11), P < 0.001. Effect sizes for OLS regression were intermediate to those for quantiles 0.05 and 0.50. CONCLUSIONS.Risk factors for myopia were associated with much larger effects in children in the extremes of the refractive error distribution, providing indirect evidence that emmetropization buffers against both genetic and environmental risk factors.

Whole exome sequence analysis in 51 624 participants identifies novel genes and variants associated with refractive error and myopia

“…However, refractive errors are highly heritable, and genome-wide association studies (GWASs) have identified >450 different regions of the human genome that confer susceptibility to refractive error ( 6 , 7 ). Consistent with this evidence for a role of both genetic and lifestyle factors, recent studies suggest that specific genetic variants act as risk factors for myopia in individuals who are exposed to a high-risk environment, such as intensive education, via gene–environment interaction ( 8 , 9 ). Monogenic forms of high myopia and high hyperopia have also been identified in which a high penetrance allele of large effect is present alongside the polygenic background ( 10 , 11 ).…”

Combination Effect of Outdoor Activity and Screen Exposure on Risk of Preschool Myopia: Findings From Longhua Child Cohort Study

“…As myopia progresses most rapidly in younger children, this could have a great impact on the ultimate amount of myopia that develops ( 54 ). It could also provide a buffer to reduce the impact of upcoming educational pressure and increased near work on myopia ( 55 ). Further birth cohort studies are needed to verify the effect of avoiding screen use and going outdoor more frequently on myopia risk and also to explore the underlying mechanism.…”

Evaluation of Shared Genetic Susceptibility to High and Low Myopia and Hyperopia

“…Third, the analyses assumed that genetic variants acted additively, and they ignored t h e i n fl u e n c e o f ge n e -e nv i ro n m e nt a n d e p i s t at i c interactions. 15,45,46 Previous work 21,29 has demonstrated that genetic risk for myopia is shared between individuals of European and Asian ancestry. Coupled with the current findings, this suggests that many recent molecular genetic studies of myopia are of limited value.…”