Relative genetic and environmental contributions to variations in electroretinogram responses quantified in a twin study

Abstract

Purpose : To estimate heritability of parameters of human retinal electrophysiology in a classic twin study, and explore changes with age.

Methods : Adult monozygotic (MZ) and dizygotic (DZ) twin pairs were recruited from the TwinsUK cohort. Electroretinogram (ERG) responses were recorded using conductive fibre electrodes in response to stimuli incorporating standards set by the International Society for the Clinical Electrophysiology of Vision (ISCEV). ISCEV parameters were extracted, and, in addition, photopic negative response (PhNR, originating from retinal ganglion cells) and i-wave components were extracted from responses to the photopic single flash. Parameter values were averaged from both eyes. Mean values were calculated for the cohort. Coefficients of correlations with age were calculated (using one twin from each pair). Coefficients of intra-pair correlation were calculated for MZ and DZ twins. Age-adjusted heritability estimates were derived using structural equation modelling.

Results :
Responses were recorded from 210 participants (59 MZ and 46 DZ twin pairs). 93% were female. Mean (SD) age was 62.4 (11.4) years. In general, age correlated negatively with response amplitudes, and positively with implicit times. Correlations were statistically significant (p<0.05) and moderate or strong (coefficient >0.35) for the following parameters: scotopic standard and bright flash a-wave implicit times; photopic 30 Hz flicker and single flash b-wave implicit times; PhNR and i-wave implicit times. Intra-pair correlations were higher for MZ than DZ twins, suggesting important genetic influences. Age-adjusted estimates of heritability were significant for all parameters (except scotopic dim flash b-wave implicit time), ranging from 0.34 to 0.85. Highest estimates were for photopic single flash a-wave and b-wave amplitudes (0.84 and 0.85 respectively).

Conclusions : Most parameters showed significant heritability indicating genetic factors are important, determining up to 85% of the variance in some cone system response parameters. Parameters relating to retinal ganglion cell function were also heritable, and showed increasing delay with age. Scotopic responses tended to show lower heritability (possibly relating to greater rod system susceptibility to environmental factors).

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.