Importantly, polygenic susceptibility to obesity can influence monogenic obesity penetrance and the phenotypes of rare variants carriers: for instance, carriers of monoallelic, pathogenic mutations in MC4R with a low polygenic risk score (bottom quartile) have an approximately 5-kg/m2 lower BMI (approximately 14 kg of body weight for a 1.7-m-tall person) than those with a high PRS (top quartile) [57]. This evidence concerns the gene MC4R and obesity due to melanocortin 4 receptor deficiency.