MC4R is recognized for harboring rare and common variants associated with obesity22,23 and T2D13,24; however, its rare variant association with youth-onset T2D had a 1.75-fold larger effect size and was an order of magnitude more significant than previously observed for adult-onset T2D13 (adult-onset OR 2.07, P = 2.7×10− 10, N = 20,791 cases). Here, MC4R is linked to type 2 diabetes mellitus.