Evidence that emmetropization buffers against both genetic and environmental risk factors for myopia
Yes ; 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: Avon Longitudinal 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. ; UK Medical Research Council and Wellcome (grant ref: 102215/2/13/2), and the University of Bristol provided core support for ALSPAC. This research was specifically funded by the UK National Eye Research Centre (grant SAC015), the Global Education Program of the Russian Federation government, a PhD studentship grant from the UK College of Optometrists ("Genetic Prediction of Individuals At-Risk for Myopia Development"), and an NIHR Senior Research Fellowship award SRF-2015-08-005. The Generation R study is supported by the Erasmus Medical Center, Rotterdam, Erasmus University, Rotterdam, the Netherlands; the Netherlands Organization of Scientific Research (NWO); Netherlands Organization for the Health Research and Development (ZonMw); the Ministry of Education, Culture and Science; the Ministry for Health,Welfare and Sports; the European Commission (DG XII); European Research Council (ERC) under the European Union's Horizon 2020 Research and Innovation Programme (grant 648268); the Netherlands Organization for Scientific Research (NWO, grant 91815655); and Oogfonds, ODAS, Uitzicht 2017-28 (LSBS, MaculaFonds, Oogfonds).