Given the large number of nuclear-encoded mitochondrial genes (∼1,000 known based on the mitochondrial protein compendium MitoCarta [22]) and the largely unexplained genetic basis of T2D, it is possible that many (tens or hundreds of) common variants in or near mitochondrial genes are associated with T2D. While each gene might have a modest effect too small to be detected on its own, together they could have a more substantial collective impact. It is also possible that several nuclear regulators of mitochondrial genes could harbor common variants of modest effects on T2D risk.
