Thyroid Research Thyroid Research Archive Graves' Disease

Concordance of Graves' disease is greater in monozygotic than dizygotic twins

(November 2002)

The background of the study. There is evidence for genetic susceptibility to Graves' disease, based on studies of twins and family clustering, but the degree of heritability varied in different studies. In this study the heritability of Graves' disease was determined in large groups of monozygotic (identical) and dizygotic (nonidentical) twins.

How the study was done. A file containing the names of all twins born in California from 1908 to 1982 was linked to the state's file of people who had driver's licenses in 1991; this linkage yielded 102,000 twins. A questionnaire was then sent to the 36,244 twins aged 40 years or older. The twins were asked about their medical history, including questions about Graves' disease and other thyroid disease in themselves, their twins, and other family members. Questionnaires were returned by 19,378 people (53 percent), representing 13,708 twin pairs. Based on the replies, 32 percent were monozygotic twins, 37 percent were like-sex dizygotic twins, and 31 percent were unlike-sex dizygotic twins. More detailed thyroid-related information was obtained by telephone interview from the people who reported a diagnosis of Graves' or other thyroid disease. An investigator who did not know the respondent's identity and twin status reviewed each questionnaire to make a final diagnosis.

The results of the study. Based on the initial questionnaire, a diagnosis of Graves' disease was suggested in 118 members of 110 twin pairs. Information was available from both twins of 62 twin pairs, of whom 70 had Graves' disease, and one twin of 48 twin pairs, of whom 35 had Graves' disease and 13 reported it in their twin.

Among these 118 people, 106 (77 women, 29 men) were considered to have Graves' disease after the telephone interview. Ten had no twin at risk, because of death or thyroidectomy. Among the 89 twin pairs in which one or both twins had Graves' disease, there were 35 pairs of monozygotic twins, among which 6 pairs (17 percent) were concordant for Graves' disease. There were 54 pairs of dizygotic twins, among which 1 pair (2 percent) was concordant for Graves' disease. In the twin pairs concordant for Graves' disease the average age at diagnosis was 33 years (range, 12 to 46), and the mean interval between diagnosis in each member of a pair was 12 years. None of the twins with Graves' disease had a spouse with the disease, but 19 of 488 immediate family members (4 percent) did have the disease.

The conclusions of the study. The higher frequency of Graves' disease in monozygotic than in dizygotic twins confirms that the disease has a heritable component.

The original article. Ringold DA, Nicoloff JT, Kesler M, Davis H, Hamilton A, Mack T. Further evidence for a strong genetic influence on the development of autoimmune thyroid disease: the California Twin Study. Thyroid 2002;12:647-53.