Common nonsynonymous variants in PCSK1 confer risk of obesity Academic Article uri icon

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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

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

publication date

  • August 2008