A genetic risk score and number of myopic parents independently predict myopia

Ophthalmic Physiol Opt. 2018 Sep;38(5):492-502. doi: 10.1111/opo.12579. Epub 2018 Sep 4.

Abstract

Purpose: To investigate whether a genetic risk score (GRS) improved performance of predicting refractive error compared to knowing a child's number of myopic parents (NMP) alone.

Methods: This was a retrospective analysis of data from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort study. Refractive error was assessed longitudinally between age 7-15 using non-cycloplegic autorefraction. Genetic variants (n = 149) associated with refractive error from a Consortium for Refractive Error And Myopia (CREAM) genome-wide association study were used to calculate a GRS for each child. Using refractive error at ages 7 and 15 years as the outcome variable, coefficient of determination (R2 ) values were calculated via linear regression models for the predictors: NMP, GRS and a combined model.

Results: Number of myopic parents was weakly predictive of refractive error in children aged 7 years, R2 = 3.0% (95% CI 1.8-4.1%, p < 0.0001) and aged 15 years, R2 = 4.8% (3.1-6.5%, p < 0.0001). The GRS was also weakly predictive; age 7 years, R2 = 1.1% (0.4-1.9%, p < 0.0001) and 15 years R2 = 2.6% (1.3-3.9%, p < 0.0001). Combining the 2 variables gave larger R2 values at age 7, R2 = 3.7% (2.5-5.0%, p < 0.0001) and 15, R2 = 7.0% (5.0-9.0%, p < 0.0001). The combined model improved performance at both ages (both p < 0.0001).

Conclusion: A GRS improved the ability to detect children at risk of myopia independently of knowing the NMP. We speculate this may be because NMP captures information concerning environmental risk factors for myopia. Nevertheless, further gains are required to make such predictive tests worthwhile in the clinical environment.

Keywords: ALSPAC; genetic prediction; myopia; refractive error.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Female
  • Follow-Up Studies
  • Genetic Testing / methods*
  • Genome-Wide Association Study*
  • Humans
  • Incidence
  • Male
  • Myopia / diagnosis
  • Myopia / epidemiology
  • Myopia / genetics*
  • Predictive Value of Tests
  • Refraction, Ocular / physiology*
  • Retrospective Studies
  • Risk Factors
  • United Kingdom / epidemiology