Genetic epidemiology of glaucoma endophenotypes : a twin study.

Abstract

Glaucoma is the second leading cause of blindness worldwide. The aim of this project was to examine the genetic epidemiology of endophenotypes or intermediate phenotypes, which play a role in glaucoma. Twin studies, by comparing the concordance of phenotypes in monozygotic and dizygotic twin pairs, can be used to determine the relative importance of genes and environment in eye disease. In total, 574 twin pairs were examined (271 monozygotic and 303 dizygotic). Twins, who volunteered for this study; mainly through media campaigns, were unaware of any potential eye study. Three classical twin studies were performed on intraocular pressure, optic disc parameters and corneal hysteresis with ocular pulse amplitude, respectively. Measurements were performed using the Goldmann Applanation Tonometer, Ocular Response Analyser and Dynamic Contour Tonometer. In addition, optic disc photographs were taken using the Nidek-3DX Stereo Camera. Besides the heritability studies, a comparison study between the three tonometers was performed, together with an analysis of the effect of using the mean of several measures on heritability estimates. A preliminary genome wide scan was also performed on intraocular pressure, using the data from this study. The heritability of intraocular pressure was 63%, optic disc area 83%, optic cup area 68% and optic rim area 38%. The heritability of corneal hysteresis was 76% and of ocular pulse amplitude 63%. This suggests that genes are important in these endophenotypes and this was confirmed by genetic modelling. In conclusion, the heritability of these parameters was found to be substantial and a preliminary genome wide analysis showed areas of potential loci for intraocular pressure. These results encourage the identification of susceptibility genes through further genetic analysis.