One way to test whether mitochondrial genes play a causal role in the pathogenesis of T2D is to search for inherited DNA variants in mitochondrial genes that influence T2D risk. Proof of concept comes from rare mutations in mitochondrial DNA (mtDNA) that cause Maternally Inherited Diabetes with Deafness (OMIM #520000). This raises the question of whether inherited variants affecting mitochondrial biology play a more general causal role in the common form of T2D. Candidate gene studies of mitochondria-related genes have yet to conclusively demonstrate (at genome-wide significance) that common variants in nuclear-encoded mitochondrial genes or transcriptional regulators of mitochondrial genes associate with T2D risk [13]–[15]. Also, we published a systematic scan for associations of common single-nucleotide polymorphisms (SNPs) in mtDNA (that encodes 13 genes) that failed to identify significant associations with T2D [16].
