It was previously demonstrated that the genetic effects of variants associated with either insulin secretion (like for GCK, KCNJ11 or TCF7L2) or insulin action (for ENPP1, ADIPOQ or PPARG) may be modulated by the obesity status or adiposity [9,12,26,28,32,34]. The gene discussed is TCF7L2; the disease is obesity due to melanocortin 4 receptor deficiency.