The genetics of type 2 diabetes: what have we learned from GWAS?

Type 2 diabetes mellitus has been at the forefront of human diseases and phenotypes studied by new genetic analyses. Thanks to genome-wide association studies, we have made substantial progress in elucidating the genetic basis of type 2 diabetes. This review summarizes the concept, history, and recent discoveries produced by genome-wide association studies for type 2 diabetes and glycemic traits, with a focus on the key notions we have gleaned from these efforts. Genome-wide association findings have illustrated novel pathways, pointed toward fundamental biology, confirmed prior epidemiological observations, drawn attention to the role of β-cell dysfunction in type 2 diabetes, explained ~10% of disease heritability, tempered our expectations with regard to their use in clinical prediction, and provided possible targets for pharmacotherapy and pharmacogenetic clinical trials. We can apply these lessons to future investigation so as to improve our understanding of the genetic basis of type 2 diabetes.