While the above findings show no evidence of association between relevant mitochondrial gene sets and T2D, these genes could still display causal associations with specific intermediate phenotypes linked to the disease. Support for this comes from reported mitochondrial dysfunction in insulin-resistant individuals [8]. Therefore, we tested the same three gene sets described above for enrichment of associations with seven different glucose and insulin-related traits characteristic of T2D, using GWA meta-analyses of up to 46,186 non-diabetic individuals [37], [38] (Soranzo N. et al., unpublished data). The quantitative traits analyzed include fasting levels of glucose and insulin, glucose and insulin levels 2 hours following a 75-gram oral glucose tolerance test, indices of β-cell function (HOMA-B) and insulin resistance (HOMA-IR) [49], and glycated hemoglobin levels (HbA1C), which reflect long-term plasma glucose concentrations (see Materials and Methods).
