In this study, we replicated the finding that carriers of two gain-of-function (GoF) MC4R variants (Val103Ile and Ile251Leu) had a lower BMI25 and also found that they had a favorable metabolic profile characterized by higher HDL-cholesterol, lower TGs and lower glycated hemoglobin; we did not observe any significant impact of these GoF variants on LDL-cholesterol levels, blood pressure or coronary artery disease risk in either BMI-unadjusted or BMI-adjusted models (Supplementary Tables 12 and 13). This evidence concerns the gene MC4R and coronary artery disorder.