MC4R and obesity due to melanocortin 4 receptor deficiency: We identified (a) monogenic diabetes variants in 2.1% of individuals; (b) two exome-wide significant (P < 4.3×10−7) common coding variant associations (in WFS1 and SLC30A8); (c) three exome-wide significant (P < 2.5×10−6) rare variant gene-level associations (HNF1A, MC4R, ATX2NL); and (d) rare variant association enrichments within 25 gene sets broadly related to obesity, monogenic diabetes, and β-cell function.