Further Evidence for a Strong Genetic Influence on the Development of Autoimmune Thyroid Disease: The California Twin Study

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Abstract
To determine the heritable component of Graves' disease (GD) more precisely, a disease survey questionnaire completed by 13,726 California-born twin pairs over the age of 37 years was used as the foundation of this study. On the basis of this survey, each member of pairs reporting a past diagnosis of GD was then sought for an extensive telephone interview to seek diagnostic confirmation. Successful diagnostic evaluation occurred in 108 cases, of which 99 affected twin pairs form the basis of this report. The results indicate that the estimated pairwise concordance for is 17% in monozygotic (MZ) twins, and 1.9% in dizygotic (DZ) twins, which are in close agreement with a recent report from a Danish twin population. Moreover, the reported 3.9% occurrence of GD found in the first-degree relatives of affected twin pairs supports these findings. In contrast, only 0.45% of all twins, 0.27% of the spouses of twins, and approximately 0.16% of the first-degree relatives of unaffected twins were reported to have GD. Additionally, among the unaffected MZ twins of patients with GD, 17% reported having chronic thyroiditis and 10% other nonthyroid autoimmune conditions such as lupus erythematosus, pernicious anemia, or idiopathic thrombocytopenic purpura. Thus, a genetic predisposition appears to be shared for both thyroid and some nonthyroid autoimmune diseases. While it seems that GD is a strongly and nonspecifically heritable condition, the relatively low level of twin concordance indicates that this disease likely requires a nonheritable etiologic determinant(s) as well.