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.
Benzinou
Michael
M
Genomic Medicine, Imperial College London, Hammersmith Hospital, London W120NN, UK.
Creemers
John W M
JW
Choquet
Helene
H
Lobbens
Stephane
S
Dina
Christian
C
Durand
Emmanuelle
E
Guerardel
Audrey
A
Boutin
Philippe
P
Jouret
Beatrice
B
Heude
Barbara
B
Balkau
Beverley
B
Tichet
Jean
J
Marre
Michel
M
Potoczna
Natascha
N
Horber
Fritz
F
Le Stunff
Catherine
C
Czernichow
Sebastien
S
Sandbaek
Annelli
A
Lauritzen
Torsten
T
Borch-Johnsen
Knut
K
Andersen
Gitte
G
Kiess
Wieland
W
Körner
Antje
A
Kovacs
Peter
P
Jacobson
Peter
P
Carlsson
Lena M S
LM
Walley
Andrew J
AJ
Jørgensen
Torben
T
Hansen
Torben
T
Pedersen
Oluf
O
Meyre
David
D
Froguel
Philippe
P
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
D045664:Proprotein Convertase 1