The psPRS for Obesity from hard-clustering (Fig. 3a, b and ESM Table 13) was significantly associated with a higher incidence of clinical requirement of insulin treatment (HR 1.09 [95% CI 1.05, 1.13], p= 9.3×10−6) and insulin initiation (HR 1.05 [95% CI 1.01, 1.08], p=0.0050). This evidence concerns the gene INS and obesity due to melanocortin 4 receptor deficiency.