Common nonsynonymous variants in PCSK1 confer risk of obesity.

• Mutations in PCSK1 cause monogenic obesity. To assess the contribution of PCSK1 to polygenic obesity risk, we genotyped tag SNPs in a total of 13,659 individuals of European ancestry from eight independent case-control or family-based cohorts. The nonsynonymous variants rs6232, encoding N221D, and rs6234-rs6235, encoding the Q665E-S690T pair, were consistently associated with obesity in adults and children (P = 7.27 x 10(-8) and P = 2.31 x 10(-12), respectively). Functional analysis showed a significant impairment of the N221D-mutant PC1/3 protein catalytic activity.

Nyckelord

Adult

Case-Control Studies

Child

European Continental Ancestry Group

Genetic Predisposition to Disease

Humans

Obesity

genetics

metabolism

Polymorphism

Single Nucleotide

Proprotein Convertase 1

genetics

metabolism

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)