In contrast, we found that GoF MC4R variants were strongly associated with lower BMI (p = 2 × 10−47) and lower odds of obesity (p = 3 × 10−38), severe obesity (p = 1 × 10−09), type 2 diabetes (p = 4 × 10−06), and coronary artery disease (p = 0.02) (Figure 1E). Here, MC4R is linked to obesity due to melanocortin 4 receptor deficiency.