Abstract
Purpose :
Retinal signalling appears to be important in the process of emmetropisation. A large number of genetic loci associated with myopia risk have now been identified. We explored associations between myopia-risk polymorphisms and light-adapted flicker electroretinogram (ERG) responses recorded in healthy adult twins.
Methods :
This study analysed light-adapted 30 Hz flicker ERG peak times recorded in two non-overlapping cohorts recruited from the TwinsUK registry. Cohort 1 comprised 786 genotyped subjects who had undergone non-mydriatic ERG recording with skin electrodes (RETeval system, LKC technologies, Gaithersburg, MD) to stimuli designed to deliver retinal illuminance equivalent to the international standard 30 Hz ERG. Cohort 2 comprised 185 twins who had undergone conventional standard mydriatic 30 Hz ERG recording (Colordome, Diagnosys LLC, Lowell, MA) with conductive fibre electrodes following mydriasis and at least 10 min light adaptation to the standard light-adapting background. Phenotypes were normalised and standardised. Linear mixed models, adjusting for age, sex and familiar relatedness were used to test associations between 334 myopia risk loci and ERG peak times (Cohort 1). Associations of interest were then tested specifically in Cohort 2. We pooled the results from each through a fixed-effect inverse variance meta-analysis.
Results :
No genetic associations reached statistical significance after correction for multiple testing in Cohort 1. However, one of the loci reaching nominal significance was rs13268738 (p=0.0148) which is within the CNGB3 gene, encoding one of the subunits of the outer segment cation channel which underlies the cone photoreceptor electrical response to light. This single association was tested in ERGs from Cohort 2 and found to be significant (p=0.00526). The direction of associations was consistent, and it became more statistically significant after a meta-analysis.
Conclusions :
Although the association was only nominally significant in Cohort 1, the replication in Cohort 2 strengthens the evidence that this locus is associated with retinal cone-driven flicker responses in healthy individuals. The findings are consistent with alterations in cone-driven signals playing a role in myopia development.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.