Common nonsynonymous variants in PCSK1 confer risk of obesity.

Research output: Contribution to journalJournal articleResearchpeer-review

Michael Benzinou, John W M Creemers, Helene Choquet, Stephane Lobbens, Christian Dina, Emmanuelle Durand, Audrey Guerardel, Philippe Boutin, Beatrice Jouret, Barbara Heude, Beverley Balkau, Jean Tichet, Michel Marre, Natascha Potoczna, Fritz Horber, Catherine Le Stunff, Sebastien Czernichow, Annelli Sandbæk, Torsten Lauritzen, Knut Borch-Johnsen & 12 others Gitte Andersen, Wieland Kiess, Antje Körner, Peter Kovacs, Peter Jacobson, Lena M S Carlsson, Andrew J Walley, Torben Jørgensen, Torben Hansen, Oluf Pedersen, David Meyre, Philippe Froguel

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.
Original languageEnglish
JournalNature Genetics
Volume40
Issue number8
Pages (from-to)943-5
Number of pages2
ISSN1061-4036
DOIs
Publication statusPublished - 2008

Bibliographical note

Keywords: Adult; Case-Control Studies; Child; European Continental Ancestry Group; Genetic Predisposition to Disease; Humans; Obesity; Polymorphism, Single Nucleotide; Proprotein Convertase 1

ID: 8466806