Endocrine Abstracts

Autoimmune thyroid disease (AITD) is the commonest of the autoimmune disorders. Strong familial clustering supports a hereditary component to the development of disease. However, the pattern of inheritance suggests that many genes with relatively small effect size are contributing to the genetic architecture of both Graves’ disease and autoimmune hypothyroidism. Whilst early candidate gene studies helped to identify some of the major effects conferring risk to AITD, including the HLA status of an individual and other genes involved in regulating the immune system, such as CTLA4 and PTPN2, many loci remained unknown. In the last 5 years or so, new technologies and large DNA collections have facilitated the use of genome-wide association studies in many common diseases in which over 500 000 genetic markers have been examined in many thousands of people with disease. This approach has focused on the study of the most common variants in the human genome, namely single nucleotide polymporhism (SNPs), and delivered many new disease-risk genes, including for Graves’ disease a more detailed understanding of the TSHR locus. The most recent studies have also looked at other DNA variants such as common number variants (CNVs) and large scale detailed resequencing of the genome. Through these efforts we have made significant advances in our understanding of the genes that confer risk to many common diseases including AITD. Many loci however, remain undetected. Moreover, one of major challenges ahead will be trying to understand the functional consequences of the DNA variants conferring risk to disease.