Common nonsynonymous variants in PCSK1 confer risk of obesity

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 Sandbaek; Torsten Lauritzen; Knut Borch-Johnsen; 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

doi:10.1038/ng.177

Common nonsynonymous variants in PCSK1 confer risk of obesity

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 Sandbaek
, Torsten Lauritzen
, Knut Borch-Johnsen

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^*

^*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskrift › Artikel › Forskning › peer review

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.

Originalsprog	Engelsk
Sider (fra-til)	943-945
Antal sider	3
Tidsskrift	Nature Genetics
Vol/bind	40
Udgave nummer	8
DOI	https://doi.org/10.1038/ng.177
Status	Udgivet - 1 aug. 2008

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Benzinou, M., Creemers, J. W. M., Choquet, H., Lobbens, S., Dina, C., Durand, E., Guerardel, A., Boutin, P., Jouret, B., Heude, B., Balkau, B., Tichet, J., Marre, M., Potoczna, N., Horber, F., Le Stunff, C., Czernichow, S., Sandbaek, A., Lauritzen, T., ... Froguel, P. (2008). Common nonsynonymous variants in PCSK1 confer risk of obesity. Nature Genetics, 40(8), 943-945. https://doi.org/10.1038/ng.177

@article{842665abc9324d97a5c5b370300ae8f1,

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 {\texttimes} 10-8 and P = 2.31 {\texttimes} 10-12, respectively). Functional analysis showed a significant impairment of the N221D-mutant PC1/3 protein catalytic activity.",

author = "Michael Benzinou and Creemers, \{John W.M.\} and Helene Choquet and Stephane Lobbens and Christian Dina and Emmanuelle Durand and Audrey Guerardel and Philippe Boutin and Beatrice Jouret and Barbara Heude and Beverley Balkau and Jean Tichet and Michel Marre and Natascha Potoczna and Fritz Horber and \{Le Stunff\}, Catherine and Sebastien Czernichow and Annelli Sandbaek and Torsten Lauritzen and Knut Borch-Johnsen and Gitte Andersen and Wieland Kiess and Antje K{\"o}rner and Peter Kovacs and Peter Jacobson and Carlsson, \{Lena M.S.\} and Walley, \{Andrew J.\} and Torben J{\o}rgensen and Torben Hansen and Oluf Pedersen and David Meyre and Philippe Froguel",

year = "2008",

month = aug,

day = "1",

doi = "10.1038/ng.177",

language = "English",

volume = "40",

pages = "943--945",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

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Benzinou, M, Creemers, JWM, Choquet, H, Lobbens, S, Dina, C, Durand, E, Guerardel, A, Boutin, P, Jouret, B, Heude, B, Balkau, B, Tichet, J, Marre, M, Potoczna, N, Horber, F, Le Stunff, C, Czernichow, S, Sandbaek, A, Lauritzen, T, Borch-Johnsen, K, Andersen, G, Kiess, W, Körner, A, Kovacs, P, Jacobson, P, Carlsson, LMS, Walley, AJ, Jørgensen, T, Hansen, T, Pedersen, O, Meyre, D & Froguel, P 2008, 'Common nonsynonymous variants in PCSK1 confer risk of obesity', Nature Genetics, bind 40, nr. 8, s. 943-945. https://doi.org/10.1038/ng.177

TY - JOUR

T1 - Common nonsynonymous variants in PCSK1 confer risk of obesity

AU - Benzinou, Michael

AU - Creemers, John W.M.

AU - Choquet, Helene

AU - Lobbens, Stephane

AU - Dina, Christian

AU - Durand, Emmanuelle

AU - Guerardel, Audrey

AU - Boutin, Philippe

AU - Jouret, Beatrice

AU - Heude, Barbara

AU - Balkau, Beverley

AU - Tichet, Jean

AU - Marre, Michel

AU - Potoczna, Natascha

AU - Horber, Fritz

AU - Le Stunff, Catherine

AU - Czernichow, Sebastien

AU - Sandbaek, Annelli

AU - Lauritzen, Torsten

AU - Borch-Johnsen, Knut

AU - Andersen, Gitte

AU - Kiess, Wieland

AU - Körner, Antje

AU - Kovacs, Peter

AU - Jacobson, Peter

AU - Carlsson, Lena M.S.

AU - Walley, Andrew J.

AU - Jørgensen, Torben

AU - Hansen, Torben

AU - Pedersen, Oluf

AU - Meyre, David

AU - Froguel, Philippe

PY - 2008/8/1

Y1 - 2008/8/1

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/48349113289

U2 - 10.1038/ng.177

DO - 10.1038/ng.177

M3 - Article

C2 - 18604207

AN - SCOPUS:48349113289

SN - 1061-4036

VL - 40

SP - 943

EP - 945

JO - Nature Genetics

JF - Nature Genetics

IS - 8

ER -

Common nonsynonymous variants in PCSK1 confer risk of obesity

Abstract

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