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 Sandbæk; 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 Sandbæk, Torsten Lauritzen, Knut Borch-JohnsenGitte 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

221 Citations (Scopus)

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.

Original language	English
Journal	Nature Genetics
Volume	40
Issue number	8
Pages (from-to)	943-5
Number of pages	2
ISSN	1061-4036
DOIs	https://doi.org/10.1038/ng.177
Publication status	Published - 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., Sandbæk, A., Lauritzen, T., ... Froguel, P. (2008). Common nonsynonymous variants in PCSK1 confer risk of obesity. Nature Genetics, 40(8), 943-5. https://doi.org/10.1038/ng.177

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, Sandbæk, 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, vol. 40, no. 8, pp. 943-5. https://doi.org/10.1038/ng.177

@article{636a9400acda11ddb538000ea68e967b,

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.",

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 Sandb{\ae}k 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",

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

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doi = "10.1038/ng.177",

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pages = "943--5",

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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 - Sandbæk, 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

N1 - Keywords: Adult; Case-Control Studies; Child; European Continental Ancestry Group; Genetic Predisposition to Disease; Humans; Obesity; Polymorphism, Single Nucleotide; Proprotein Convertase 1

PY - 2008

Y1 - 2008

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 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.

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 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.

U2 - 10.1038/ng.177

DO - 10.1038/ng.177

M3 - Journal article

C2 - 18604207

SN - 1061-4036

VL - 40

SP - 943

EP - 945

JO - Nature: New biology

JF - Nature: New biology

IS - 8

ER -

Common nonsynonymous variants in PCSK1 confer risk of obesity.

Abstract

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