Hashimoto Thyroiditis and Graves Disease: Little Genetic Overlap

Little genetic evidence exists to justify grouping Hashimoto thyroiditis (HT) and Graves disease (GD) as a single “autoimmune thyroid disease.” These findings from a national health twin registry were published in The Journal of Clinical Endocrinology and Metabolism.

Data from the Swedish Twin Registry were analyzed for this study. Swedish twins born from 1886 and beyond have been recorded in this registry, and in 1964, inpatient information began to be incorporated. Twins (N=110,814) who were both alive or not yet born in 1976 with established zygosity were assessed for diagnoses of HT or GD or both.

A total of 1683 (1.5%) were diagnosed with HT, 558 (0.5%) with GD, and 15 with both.

HT and GD were more common among women (24.0 per 1000; 8.9 per 1000) than men (5.2 per 1000; 1.8 per 1000), respectively. Gender-specific heritability for HT was 90% among men and 60% among women (P <.001). The heritability of GD was similar among both men and women (79% vs 63%; P =.085), respectively.

Among monozygotic twins, the risk for developing HT (adjusted hazard ratio [aHR], 11.8; 95% CI, 8.9-15.7) or GD (aHR, 33.8; 95% CI, 19.2-59.6) was increased if their co-twin had received a diagnosis. Among men, the likelihood of both twins receiving an HT (aHR, 126.9; 95% CI, 59.1-272.5) or GD (aHR, 113.9; 95% CI, 27.6-469.7) diagnosis was particularly elevated.

The risk for receiving a GD diagnosis when their co-twin had HT (aHR, 3.3; 95% CI, 1.3-8.0) or an HT diagnosis when their co-twin had GD (aHR, 3.5; 95% CI, 1.9-6.4) was lower than receiving the same diagnosis.

Similar but more subtle patterns were observed among dizygotic twins.

The additive genetic effect shared among twins with HT was 0.08 (95% CI, 0.01-0.15) and 0.08 (95% CI, 0.01-0.14) for GD. The environmental effect shared among twins with HT was 0.11 (95% CI, -0.02 to 0.24) and 0.11 (95% CI, -0.02 to 0.25) for GD.

This study may have been limited by not including biochemical data, making misdiagnoses possible among the studied twins.

These findings indicated there was only a modest overlap of genetic and environmental factors among twins with HT or GD, indicating these diseases may be distinct entities. Further study is needed.  

Reference

Skov J, Calissendorff J, Eriksson D, et al. Limited genetic overlap between overt Hashimoto’s thyroiditis and Graves’ disease in twins: a population-based study. J Clin Endocrinol Metab. 2020;dgaa956. doi:10.1210/clinem/dgaa956