Abstract
Purpose :
Refractive errors and the age of first wearing glasses or contact lenses are correlated both observationally and at a genotypic level. Individuals who require vision correction at an earlier age often progress to high-grade myopia, and thus are at a greater risk of complications. The purpose is to identify genetic risk factors associated with the age of first spectacle wear in a large genome-wide association study.
Methods :
For the purposes of this work, we conducted a survival analysis in the age of first spectacle or contact lens correction. This phenotype was available for 340,419 UK Biobank participants of European descent, self-reported through an electronic questionnaire. In addition, direct phenotypic information about spherical equivalent and other ocular measurements were available for a subset of participants (N=90,550). The genetic associations with the age of first spectacle wear were tested using Cox proportional hazards-ratios model, adjusted for age and sex.
Results :
We found genetic associations with 44 independent genetic regions, most of which previously associated with refractive error. The strongest association was observed for TSPAN10 (p=1.71x10-35). Although an early onset of refractive correction correlated well with spherical equivalent in adulthood, several genes such as PRSS56, LAMA2, RDH5 had stronger effects and led to earlier manifest refractive errors, while other genes, such as AGPS, contributed to stronger than expected later life refractive error.
We were able to identify six loci at genome-wide significance, not previously reported as associated with refractive error, for example, LOC100287944 (p=1.96x10-08), and successfully validated four of them in an independent cohort.
Conclusions :
This study confirmed the correlation between age of first spectacle wear and magnitude of refractive errors. In addition, this study identified genes associated specifically with early and late-onset refractive errors which may improve understanding of the mechanisms affecting spherical equivalent measurements in the general population.
Our study also illustrates the additional power gained by the use of longitudinal and survival methodologies and contributed several novel associations with refractive error traits, adding to our knowledge of the genetic risk architecture of these conditions.
This is a 2021 ARVO Annual Meeting abstract.