Abstract
Purpose :
The discordant identical twin model can be used to examine environmental and epigenetic risk factors for diseases, as monozygotic twins share the same additive genes. The purpose of this study was to use self-reported glaucoma to establish its concordance in monozygotic (MZ) and dizygotic (DZ) twin pairs, to identify twins discordant for glaucoma, and to examine validity of the self-reported diagnosis from optic disc imaging.
Methods :
9568 adult twin volunteers aged 18-90 (mean 63 years, SD 15.8) from the population-representative TwinsUK cohort completed health questionnaires including whether they had been diagnosed with glaucoma. Questionnaires were completed from 2006-2017 and included approximately equal numbers of MZ and DZ twins. Optic disc photos and spectral-domain OCT images were examined in twins reporting glaucoma, to assess if there was supportive clinical evidence for the diagnosis (visual field data unavailable). Probandwise concordance was calculated using the formula 2C/(2C+D), where C=concordant and D=discordant twin pairs.
Results :
142 twins from 120 twin pairs self-reported as having glaucoma (prevalence 1.5%, 95% CI 1.26-1.74%). After excluding 5 subjects with no information about their twin’s status, there were 66 MZ twin pairs. Of these, 14 pairs (21.2%) were concordant for glaucoma, and 52 pairs (78.8%) were discordant. Of the 54 DZ pairs, 3 pairs (5.55%) were concordant for a diagnosis, and 51 pairs (94.4%) were discordant. The resulting probandwise concordance was 0.35 for MZ twin pairs, and 0.11 for DZ twin pairs.
Retinal and OCT images were available for 72 of the 142 twins with a self-report of glaucoma. The imaging was felt to support a definite or likely diagnosis of glaucomatous optic neuropathy in only 34 (47.2%) of these subjects. For these participants, probandwise concordance was 0.5 for MZ and 0.18 for DZ twin pairs.
Conclusions :
The concordance for MZ pairs with self-reported glaucoma is significantly greater than that for DZ pairs, confirming a significant genetic component. However, in this cohort self-report of glaucoma appears unreliable, with the diagnosis being felt to be likely or definite in only just under half of the subjects. It may be easier to identify discordant MZ twins based on quantitative endophenotypes such as intraocular pressure and retinal nerve fibre layer thickness, given glaucoma is uncommon in the population and self-report unreliable.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.