Genetic epidemiology of common eye diseases: A twin study

Cataract and age-related macular degeneration are important causes of blindness and visual impairment, and refractive error is highly prevalent and considerable time and expense is directed at its correction. Epidemiological studies have identified environmental risk factors for all these condition, while other studies have demonstrated familial aggregation. Twin studies, which compare the concordance of phenotypes in monozygotic and dizygotic twin pairs, can be used to elucidate the genetic epidemiology of eye disease - i.e. determine the relative importance of genes and environment. This thesis describes a classical twin study of 506 twin pairs (280 dizygotic and 226 monozygotic) with a mean age of 62 years. When they volunteered through national media campaigns, they were unaware of a potential eye study. Twins were comprehensively ascertained for refractive error using an autorefractor, and for cataract using subjective and objective grading techniques. Age-related macular degeneration was graded from stereoscopic macular photographs. Quantitative genetic model fitting, based on comparison of the covariance (or correlation) in the phenotype measurement between monozygotic and dizygotic twin pairs, determined the heritability, which is the ratio of genetic variance to total phenotypic variance. Mean scores were similar, but monozygotic twins were more concordant than dizygotic twins, for all phenotypes. This suggested genes are important in common eye diseases, even those age-related traits such as cataract, and was confirmed by modelling. The heritability of spherical equivalent was 84-86% and that of astigmatism 42-61%. The heritability of nuclear cataract was 48% and it was 53-58% for cortical cataract, depending on the grading system used. The heritability of early age-related maculopathy was 54%. Both astigmatism and cortical cataract appear to involve dominant inheritance. The heritability of age-related eye disease is substantial, and these results encourage identification of susceptibility genes through linkage and candidate gene studies, to further understand the mechanisms of disease.