The New Perspectives on Genetic Studies of Type 2 Diabetes and Thyroid Diseases

Abstract

Recently, genome-wide association studies (GWAS) have led to the discovery of hundreds of susceptibility loci that are associated with complex metabolic diseases, such as type 2 diabetes and hyperthyroidism. The majority of the susceptibility loci are common across different races or populations; while some of them show ethnicity-specific distribution. Though the abundant novel susceptibility loci identified by GWAS have provided insight into biology through the discovery of new genes or pathways that were previously not known, most of them are in introns and the associated variants cumulatively explain only a small fraction of total heritability. Here we reviewed the genetic studies on the metabolic disorders, mainly type 2 diabetes and hyperthyroidism, including candidate genes-based findings and more recently the GWAS discovery; we also included the clinical relevance of these novel loci and the gene-environmental interactions. Finally, we discussed the future direction about the genetic study on the exploring of the pathogenesis of the metabolic diseases.

Explaining additional genetic variation in complex traits

“…Many of our current phenotypes are subjectively measured and may represent many underlying biological processes. For example, many psychiatric disorders are diagnosed on a complex range of overlapping clinical characteristics [74], type-2 diabetes is diagnosed using a blood glucose threshold [75], metabolic syndrome is based on observing three of five criteria [76], and even many quantitative traits are arbitrary metrics or defined as functions of other characters. Misclassifying a phenotype, especially when multiple distinct phenotypes are influenced by different sets of underlying causal variants, can reduce power in GWAS relative to expectation based on power calculations of idealized homogeneous populations.…”

Type 2 diabetes mellitus and thyroid disease: a two-sided analysis

“…The association between thyroid diseases, especially though autoimmune diseases, and type 1 diabetes mellitus (T1DM) is well known. However, there is an increasing mass of data from recent years showing higher prevalence of thyroid diseases also in patients with T2DM (1,2,3,4,5,6,7,8,9,10,11).…”

Jinlida Granules Improve Dysfunction of Hypothalamic-Pituitary-Thyroid Axis in Diabetic Rats Induced by STZ

“…Thyroid diseases and diabetes mellitus (DM) represent two most common endocrine disorders, both of which involve multiple organs. The common predisposing genes are detected for DM and thyroid diseases by Genome-Wide Association Study [ 1 ]. Various clinical studies suggest a significantly increased incidence of thyroid dysfunction in patients with DM [ 2 , 3 ], and one study indicates that the ratio of TT4, TT3, FT3, and TT3/rT3 in DM patients is significantly lower compared to normal group [ 4 ].…”