mitochondrial genes to T2D, we tested whether several regulators might harbor common variants with modest effect on T2D risk in the population. In our analysis we could not find strong support for this possibility. Our simulations suggest that we would have considerable power to detect enrichment if at least ∼9 OXPHOS genes or at least ∼3 nuclear regulators were modestly associated with T2D or a related trait. While specific genes ranked high among the 16 regulators (but not at gene-wide significance), such as GABPA (the GA binding protein transcription factor, alpha subunit) [50] with respect to T2D associations or SIRT1 (sirtuin, silent mating type information regulation 2 homolog 1; Entrez ID 23411) [51], [52] with respect to fasting insulin levels and measures of insulin resistance and ß-cell function, our statistical tests do not constitute a proof of their involvement in T2D. Future gene-centric approaches using our corrected gene scoring system or others may be used to examine more closely these and similar instances.
