Common nonsynonymous variants in PCSK1 confer risk of obesity
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- 6 July 2008
- journal article
- research article
- Published by Springer Nature in Nature Genetics
- Vol. 40 (8) , 943-945
- https://doi.org/10.1038/ng.177
Abstract
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 × 10−8 and P = 2.31 × 10−12, respectively). Functional analysis showed a significant impairment of the N221D-mutant PC1/3 protein catalytic activity.Keywords
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