These authors sequenced the gene for melanocortin-2 receptor accessory protein (MRAP2 ) in 9418 blood DNA samples from several population studies. They detected 23 rare heterozygous variants, which were significantly associated with an increased risk of obesity (OR 3.8 in children and 2.9 in adults). More so, functional analysis revealed a loss of function for 6 variants, with significantly decreased cAMP-PKA signalling in vitro in response to α-MSH and ACTH, and these variants showed a complete penetrance for obesity/overweight. In addition, affected carriers also showed a high rate of hyperglycemia and hypertension in contrast to carriers of other forms of monogenic obesity. None of the carriers showed hypoadrenalism.