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Common nonsynonymous variants in PCSK1 confer risk of obesity

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

in Adult / Agriculture / Amino acids / Animal Genetics and Genomics / Biological and medical sciences / Biomedical and Life Sciences / Biomedicine / brief-communication / Cancer Research / Care and treatment / Case-Control Studies / Child / European Continental Ancestry Group / Fundamental and applied biological sciences. Psychology / Gene Function / Gene mutations / Genetic aspects / Genetic Predisposition to Disease / genetics / Genetics of eukaryotes. Biological and molecular evolution / Health aspects / Human Genetics / Humans / Medical and Health Sciences / Medical sciences / Medicin och hälsovetenskap / Metabolic diseases / metabolism / Methods / Obesity / Obesity - genetics / Obesity - metabolism / Polymorphism / Polymorphism, Single Nucleotide / Proprotein Convertase 1 / Proprotein Convertase 1 - genetics / Proprotein Convertase 1 - metabolism / Risk factors / Single Nucleotide / Single nucleotide polymorphisms / Statistical analysis / Survival analysis / White People

2008

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Common nonsynonymous variants in PCSK1 confer risk of obesity

2008

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Common nonsynonymous variants in PCSK1 confer risk of obesity

2008

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Journal Article

Common nonsynonymous variants in PCSK1 confer risk of obesity

Jacobson, Peter,

Choquet, Helene,

Boutin, Philippe,

Heude, Barbara,

Carlsson, Lena M S,

Le Stunff, Catherine,

Lauritzen, Torsten,

Benzinou, Michael,

Pedersen, Oluf,

Andersen, Gitte,

Horber, Fritz,

Borch-Johnsen, Knut,

Tichet, Jean,

Walley, Andrew J,

Jørgensen, Torben,

Creemers, John W M,

Kiess, Wieland,

Balkau, Beverley,

Körner, Antje,

Meyre, David,

Potoczna, Natascha,

Kovacs, Peter,

Hansen, Torben,

Dina, Christian,

Marre, Michel,

Czernichow, Sebastien,

Durand, Emmanuelle,

Guerardel, Audrey,

Lobbens, Stephane,

Jouret, Beatrice,

Froguel, Philippe,

Sandbaek, Annelli

2008

Overview

Philippe Froguel and colleagues report that common nonsynonymous variants in PCSK1 , encoding a prohormone convertase, confer risk of obesity in individuals of European ancestry. 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.

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Publisher

Nature Publishing Group US,Nature Publishing Group

Subject

Adult

/ Agriculture

/ Amino acids

/ Animal Genetics and Genomics

/ Biological and medical sciences

/ Biomedical and Life Sciences

/ Biomedicine