Contribution of heterozygous PCSK1variants to obesity and implications for precision medicine: a case-control study

Rare biallelic pathogenic mutations in PCSK1(encoding proprotein convertase subtilisin/kexin type 1 [PC1/3]) cause early-onset obesity associated with various endocrinopathies. Setmelanotide has been approved for carriers of these biallelic mutations in the past 3 years. We aimed to perform a large-scale functional genomic study focusing on rare heterozygous variants of PCSK1to decipher their putative impact on obesity risk.