Since MTNR1B's role in the pathogenesis of human obesity and human prediabetic phenotypes, such as insulin resistance and β-cell dysfunction, was not yet assessed, it was the aim of the present study to analyse, using a HapMap approach, the association of common genetic variation (minor allele frequency, MAF>0.05) within the MTNR1B locus with state-of-the art measures of obesity, glucose tolerance, insulin sensitivity, and β-cell function in a thoroughly phenotyped population at an increased risk for type 2 diabetes. This evidence concerns the gene MTNR1B and obesity due to melanocortin 4 receptor deficiency.