The causal relevance of SERPINF2 with BMI demonstrated in both Chinese and UK adults, in addition to the evidence of a causal association with IHD and LDL-C observed in the present study, provide strong support for SERPINF2 as a likely novel target, to our knowledge, for treatment of obesity and associated diseases. Here, SERPINF2 is linked to obesity due to melanocortin 4 receptor deficiency.