MC4R and obesity due to melanocortin 4 receptor deficiency: Individuals carrying rare missense variants in MC4R (Cox proportional hazard ratio [HR] [SE] = 1.46 [0.0843], p = 7.75 × 10−6), men with pLoF variants in SLTM (HR = 5.37 [0.354], p = 2.05 × 10−6) and damaging missense variants in PCSK1 (HR = 1.86 [0.165], p = 1.63 × 10−4), and women with pLoF variants in DIDO1 (HR = 11.2 [0.578], p = 2.85 × 10−5) and SLC12A5 (HR = 14.8 [0.708], p = 1.45 × 10−4) were at risk of earlier age at onset of obesity (Figure S7; Table S7).