Limited Genetic Overlap Between Overt Hashimoto’s Thyroiditis and Graves’ Disease in Twins: A Population-based Study

CONTEXT: Hashimoto’s thyroiditis (HT) and Graves’ disease (GD) are known to coaggregate in families, but the magnitude and nature of a shared etiology is unknown. OBJECTIVES: To estimate the shared genetic influence on overt HT and GD and to examine if the heritability differs between men and women. DESIGN, SETTING, AND PATIENTS: We used national health registries to identify cases of HT and GD in a cohort of 110 814 Swedish twins. By comparing intra-class and cross-twin cross-trait correlations in dizygotic and monozygotic twins, we calculated heritability and the proportions thereof shared between the diseases. Univariate estimates of heritability were calculated by sex. RESULTS: The heritability for HT and GD was 65% (95% CI, 61-70) and 63% (95% CI, 55-72), respectively. The genetic correlation was 0.35 (95% CI, 0.20-0.50) and shared genetic effects accounted for 8% of the variance for both HT and GD. Univariate heritability was significantly higher in men than in women for HT (90% vs 60%, P < 0.001) but not for GD (79% vs 63%, P = 0.085). CONCLUSIONS: From a genetic perspective, HT and GD appear to be only modestly related diseases. Hence, the term “autoimmune thyroid disease,” used to cluster these disorders, may have limited validity in a genetic context. Moreover, the mechanisms contributing to HT are partly different for the sexes, with genetic components more important in men.