Genetics of thyroid function and disease

Genetics play a prominent role in both determination of thyroid hormone and thyrotropin (TSH) concentrations, and susceptibility to autoimmune thyroid disease. Heritability studies have suggested that up to 67% of circulating thyroid hormone and TSH concentrations are genetically determined, suggesting a genetic basis for narrow intra-individual variation in levels, perhaps a genetic 'set point'. The search for the genes responsible has revealed several candidates, including the genes for phosphodiesterase 8B, iodothyronine deiodinase 1, F-actin-capping protein subunit beta and the TSH receptor; however, each of these only contributes a small amount to the variability of hormone concentrations, suggesting that further genes and mechanisms of genetic influence are yet to be discovered. Some genes known to influence thyroid function, including iodothyronine deiodinase 2 and the TSH receptor, have been shown to influence a wide range of clinical and developmental phenotypes from bone health to neurological development and longevity; such observations will help us understand the complex action of thyroid hormones on individual tissues. Finally, autoimmune thyroid disease commonly runs in families, and the search for genes which increase susceptibility has identified several good candidates, particularly those involved in immune regulation and thyroid function. However, these genes alone account for only a small percentage of the current prevalence of these disorders. Although the advancement of genetic technology has led to many significant findings in the last decade or two, it is clear that we are only just beginning to understand the role of genetics in thyroid function and disease.