Common nonsynonymous variants in PCSK1 confer risk of obesity by Benzinou Michael, Creemers John W M, Choquet Helene, Lobbens Stephane, Dina Christian, Durand Emmanuelle, Guerardel Audrey, Boutin Philippe, Jouret Beatrice, Heude Barbara, Balkau Beverley, Tichet Jean, Marre Michel, Potoczna Natascha, Horber Fritz, Le Stunff Catherine, Czernichow Sebastien, Sandbaek Annelli, Lauritzen Torsten, Borch-Johnsen Knut, Andersen Gitte, Kiess Wieland, Körner Antje, Kovacs Peter, Jacobson Peter, Carlsson Lena M S, Walley Andrew J, Jørgensen Torben, Hansen Torben, Pedersen Oluf, Meyre David, Froguel Philippe in Nature genetics (2008).

[PMID: 18604207] PubMed


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.

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