A population-based study of Graves' disease in Danish twins

Abstract

Objective: The aetiology of Graves' disease (GD) is generally thought to fit a multi-factorial pattern of inheritance in which clinical disease develops on the basis of genetic susceptibility interacting with environmental and endogenous factors. In previous twin studies the probandwise concordance rates for hyperthyroidism were as high as 0.86 in monozygotic twins and 0.20 in dizygotic twins, indicating a very strong genetic influence. In these studies, however, no effort was made to distinguish between GD and non-autoimmune hyperthyroidism, and one study also included patients with simple non-toxic goitre, hampering if not invalidating any conclusions. The aim of the present study was to determine whether there is a genetic contribution in the aetiology of GD.

Design: Historical cohort study of pairs of same-sex twins, with information on GD being gathered by questionnaire surveys in the 1950s and 1960s. All available hospital material was sought to verify the diagnosis, which was assigned on the basis of clinical and histopathological evidence. The healthy co-twins were followed through middle age by questionnaire surveys in the 1970s and 1980s.

Patients: Same-sex twin individuals born between 1870-1920, included in a population-based nationwide register. A total of 118 subjects indicated hospitalization due to GD. A hospital record was available in 76 subjects. Of these, 55 (46 females and 9 males) could be classified as having GD.

Measurements: Pairwise and probandwise concordance rates for GD in monozygotic and dizygotic twin pairs.

Results: The probandwise concordance rates were 0.36 for monozygotic pairs and 0 for dizygotic pairs. The pairwise concordance rates were 0.22 and 0 for monozygotic and dizygotic pairs, respectively. The concordance rates were significantly (P = 0.012) higher in monozygotic than in dizygotic pairs.

Conclusions: These results confirm that genetic factors play an important role in the aetiology of Graves' disease. However, they may not be as powerful as previously thought.