The Genetic Basis of Thyroid Autoimmunity

Autoimmune thyroid diseases (AITDs), including Graves' disease (GD) and Hashimoto's thyroiditis (HT), are prevalent autoimmune diseases, affecting up to 5% of the general population. AITDs arise due to interplay between environmental and genetic factors. In the past decade, significant progress has been made in our understanding of the genetic contribution to the etiology of AITDs. Excitingly, several AITD susceptibility genes have been identified and characterized. Some of these susceptibility genes are specific to either GD or HT, while others confer susceptibility to both conditions. The first AITD susceptibility gene locus identified was the Human-Leukocyte-Antigen DR (HLA-DR) gene locus. Subsequently, a quintet of non-HLA genes, including the cytotoxic T lymphocyte antigen (CTLA-4), CD40, protein tyrosine phosphatase-22 (PTPN22), thyroglobulin, and thyroid-stimulating hormone receptor (TSHR) gene, has been shown to contribute to the susceptibility to AITDs. Recently, the mechanisms by which these new AITD genes predispose to AITDs have been dissected. In this review, we overview and highlight the recent data on the genes predisposing to AITDs and the putative mechanisms by which they confer susceptibility to disease.