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Common variants in the gene that encodes the transcription factor 7-like 2 (TCF7L2) have been strongly associated with type 2 diabetes. This highly reproducible association may uncover novel mechanisms of glycemic pathophysiology.The initial publication of an association of common variants in TCF7L2 with type 2 diabetes in people of European descent has been followed by an avalanche of replication reports. These papers not only confirm the original finding, but also extend it to other populations, fine map the source of the association signal, describe its effect on metabolic parameters in humans, open the door to a more precise molecular characterization, and provide an insight into its possible impact on diabetes therapy.The discovery of TCF7L2 as a diabetes gene illustrates that novel true diabetes genes can be found, their association with type 2 diabetes replicated and their effect incorporated into risk prediction models. It is hoped that the detection of other such genes in genome-wide association scans will help elucidate the genetic architecture of this disease.