INS and obesity due to melanocortin 4 receptor deficiency: We observed that the cardiometabolic features and loci of five of our identified clusters overlapped with those reported in previous efforts3,4,20,21, representing beta-cell dysfunction with a positive or negative association with proinsulin (PI), and insulin resistance mediated through obesity, lipodystrophy, and liver and lipid metabolism (Supplementary Table 8).