We performed whole-exome sequencing (WES) of 73 individuals with severe early-onset obesity recruited to the Genetics of Obesity Study (BMI standard deviation score [BMI SDS] > 3; age of onset below 10 years; GOOS; www.goos.org.uk), in whom known causes of monogenic obesity such as congenital leptin deficiency and MC4R deficiency had been excluded (Fig 1A, S1 Table; Methods). This evidence concerns the gene MC4R and obesity due to melanocortin 4 receptor deficiency.