Evidence for a Major Role of Heredity in Graves’ Disease: A Population-Based Study of Two Danish Twin Cohorts1

Abstract

The etiology of Graves' disease (GD), affecting up to 2% of a population in iodine-sufficient areas, is incompletely understood. According to current thinking, the development of GD depends on complex interactions among genetic, environmental, and endogenous factors. However, the relative contributions of the genetic and environmental factors remain to be clarified. In this study we report probandwise concordance rates for GD in a new cohort of same sex twin pairs born between 1953 and 1976 (young cohort), ascertained from the nationwide population-based Danish Twin Register. To elucidate the magnitude of the genetic and environmental influence in the etiology of GD, these new twin data were pooled with our previously published twin data on GD (old cohort). The old cohort consisted of 2338 same sex twin pairs born between 1870 and 1920 who had participated in questionnaire surveys during the 1950s, 1960s, and 1970s. The young cohort included 6628 same sex twin pairs born between 1953 and 1976 who had participated in a questionnaire survey in 1994. In the young cohort there were four monozygotic (MZ) pairs and one dizygotic (DZ) pair concordant for clinically overt GD, giving an overall probandwise concordance rate of 0.35 [95% confidence interval (CI), 0.16--0.57] for MZ pairs and 0.07 (95% CI, 0.01--0.24) for DZ pairs (P < 0.02). In the combined twin cohorts there were eight MZ pairs and one DZ pair concordant for clinically overt GD, giving a crude concordance rate of 0.35 (95% CI, 0.21--0.50) for MZ pairs and 0.03 (95% CI, 0.01--0.12) for DZ pairs (P < 0.02). Model-fitting analysis on the pooled twin data showed that 79% of the liability to the development of GD is attributable to genetic factors. Individual specific environmental factors not shared by the twins could explain the remaining 21%. In conclusion, our study strongly supports the idea that genetic factors play a major role in the etiology of GD and suggest that a further search for susceptibility genes is worthwhile.