Genetic liability of type 1 diabetes and the onset age among 22,650 young Finnish twin pairs: a nationwide follow-up study.

Abstract

Finland has the world's highest incidence of type 1 diabetes, and it is steadily increasing. We determined concordance rates and estimated heritability for type 1 diabetes in the Finnish Twin Cohort, a population-based twin cohort of 22,650 twin pairs. In addition, we studied age of onset in the first affected twin and discordance time between concordant twin pairs. Finnish twins born between 1958 and 1986 were followed for type 1 diabetes until 1998. We identified 228 twin pairs with type 1 diabetes: 44 monozygotic (MZ), 183 dizygotic (DZ), and 1 pair with unknown zygosity. The pairwise concordance for type 1 diabetes was 27.3% (95% CI 22.8-31.8) in MZ and 3.8% (2.7-4.9) in DZ twins. The probandwise concordance was 42.9% (26.7-59.2) and 7.4% (2.2-12.6), respectively. The longest discordance times were 6.9 years among concordant MZ twins and 23.6 years among DZ twins. The risk for type 1 diabetes was highest in cotwins of the index twins diagnosed at a very young age. The model with additive genetic and individual environmental effects was the best-fitting liability model, with 88% of phenotypic variance due to genetic factors and the remaining variance due to unshared environmental factors. In conclusion, these nationwide twin data demonstrated high genetic liability for type 1 diabetes. Early-onset diabetes increases the risk in cotwins. However, the majority of affected MZ twin pairs remain discordant for type 1 diabetes.