Methylation at 3 loci was causally linked to multiple obesity phenotypes: cg26906217 (BMI and WHR; near the PIK3C2A gene); cg15809217 (WHR, T2D and fasting insulin (FI); associated with PRRC2A expression in subcutaneous adipocytes); and cg05941027 (BMI, WHR and T2D; associated with LIMD2 expression in visceral adipocytes). Here, PIK3C2A is linked to obesity due to melanocortin 4 receptor deficiency.