TY - JOUR T1 - HMga1, a novel locus for type 2 diabetes mellitus AU - Garg A Y1 - 2011/03/02 N1 - 10.1001/jama.2011.236 JO - JAMA SP - 938 EP - 939 VL - 305 IS - 9 N2 - Both genetic and environmental factors contribute to the pathogenesis of type 2 diabetes mellitus (DM). Linkage analysis and genome-wide association studies have revealed 34 common variants (also called single-nucleotide polymorphisms) associated with type 2 DM.1 Most of the loci are associated with either abnormal insulin processing or secretion, suggesting that most of the risk of type 2 DM in the population is due to beta cell dysfunction. However, some type 2 DM loci, such as peroxisome proliferator-activated receptor gamma (PPARG) and Kruppel-like factor 14 (KLF14), indicate defective insulin action or insulin resistance as a contributor.1 In addition, some genes (eg, glucokinase [hexokinase 4] regulator, insulin-like growth factor 1 [IGF1 ], and the fat mass and obesity associated gene) are associated with fasting insulin, insulin resistance, and obesity and may also contribute to type 2 DM.1 Most of the identified variants have modest effect sizes (1.1-1.3), and all of the type 2 DM–associated variants can explain only 10% to 15% of the heritability. Thus, there is a need to identify additional novel loci for type 2 DM. One approach is to conduct large-scale meta-analyses or association analyses with common variants.2 Another is to find rare variants in candidate genes selected for their known role in biological processes related to the disease.3- 4 SN - 0098-7484 M3 - doi: 10.1001/jama.2011.236 UR - http://dx.doi.org/10.1001/jama.2011.236 ER -