We performed whole exome sequencing of 6,547 UK Biobank participants, identifying 24 rare (allele frequency < 1%) protein-altering variants in the MC4R gene. A total of 54 of the 6,547 individuals (0.8%) harbored one of these variants. Average BMI of these 54 individuals was 30.8 kg/m2 versus 28.4 kg/m2 in the remainder of the population, a difference of 2.4 kg/m2 (95% confidence interval [CI] 1.0 to 3.7; p = 0.001).
