title: Common nonsynonymous variants in PCSK1 confer risk of obesity.
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 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.
authors.affiliation: Genomic Medicine, Imperial College London, Hammersmith Hospital, London W120NN, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Benzinou
authors.forename: John W M
authors.initials: JW
authors.lastname: Creemers
authors.forename: Helene
authors.initials: H
authors.lastname: Choquet
authors.forename: Stephane
authors.initials: S
authors.lastname: Lobbens
authors.forename: Christian
authors.initials: C
authors.lastname: Dina
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Durand
authors.forename: Audrey
authors.initials: A
authors.lastname: Guerardel
authors.forename: Philippe
authors.initials: P
authors.lastname: Boutin
authors.forename: Beatrice
authors.initials: B
authors.lastname: Jouret
authors.forename: Barbara
authors.initials: B
authors.lastname: Heude
authors.forename: Beverley
authors.initials: B
authors.lastname: Balkau
authors.forename: Jean
authors.initials: J
authors.lastname: Tichet
authors.forename: Michel
authors.initials: M
authors.lastname: Marre
authors.forename: Natascha
authors.initials: N
authors.lastname: Potoczna
authors.forename: Fritz
authors.initials: F
authors.lastname: Horber
authors.forename: Catherine
authors.initials: C
authors.lastname: Le Stunff
authors.forename: Sebastien
authors.initials: S
authors.lastname: Czernichow
authors.forename: Annelli
authors.initials: A
authors.lastname: Sandbaek
authors.forename: Torsten
authors.initials: T
authors.lastname: Lauritzen
authors.forename: Knut
authors.initials: K
authors.lastname: Borch-Johnsen
authors.forename: Gitte
authors.initials: G
authors.lastname: Andersen
authors.forename: Wieland
authors.initials: W
authors.lastname: Kiess
authors.forename: Antje
authors.initials: A
authors.lastname: Körner
authors.forename: Peter
authors.initials: P
authors.lastname: Kovacs
authors.forename: Peter
authors.initials: P
authors.lastname: Jacobson
authors.forename: Lena M S
authors.initials: LM
authors.lastname: Carlsson
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Walley
authors.forename: Torben
authors.initials: T
authors.lastname: Jørgensen
authors.forename: Torben
authors.initials: T
authors.lastname: Hansen
authors.forename: Oluf
authors.initials: O
authors.lastname: Pedersen
authors.forename: David
authors.initials: D
authors.lastname: Meyre
authors.forename: Philippe
authors.initials: P
authors.lastname: Froguel
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002648:Child; D020022:Genetic Predisposition to Disease; D006801:Humans; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D045664:Proprotein Convertase 1 / Q000235:genetics* / Q000378:metabolism; D044465:White People
chemical_list: D045664:Proprotein Convertase 1