We observed particularly low penetrance of MC4R for obesity (<55% for BMI ≥ 30 kg/m2), consistent with previous findings6,39,43 (Fig. 2B) and particularly high penetrance for GCK-MODY (100% for diabetes or prediabetes in both studies, 95% CI’s 59–100% in AMP-T2D-GENES, 69–100% in UKB). Here, MC4R is linked to obesity due to melanocortin 4 receptor deficiency.