Recently, several genome-wide association (GWA) studies of ∼2,000 to 5,000 individuals [17]–[19], and a meta-analysis of 10,128 individuals [20], all of European descent, have identified ∼18 common nuclear DNA variants robustly associated with T2D that collectively explain ∼6% of the genetic contribution to T2D risk. While these associations suggest genes involved in various biological processes, such as WNT signaling, NOTCH signaling and the cell cycle, none have implicated mitochondrial processes. The only gene with a mitochondrial isoform near a validated T2D SNP is the insulin-degrading enzyme, IDE (Entrez ID 3416), but it exerts its insulin degrading activity primarily in the cytoplasm [21].
