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Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins.

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Author

  • Iris Postmus
  • Stella Trompet
  • Harshal A Deshmukh
  • Michael R Barnes
  • Xiaohui Li
  • Helen R Warren
  • Daniel I Chasman
  • Kaixin Zhou
  • Benoit J Arsenault
  • Louise A Donnelly
  • Kerri L Wiggins
  • Christy L Avery
  • Paula Griffin
  • QiPing Feng
  • Kent D Taylor
  • Guo Li
  • Daniel S Evans
  • Albert V Smith
  • Catherine E de Keyser
  • Andrew D Johnson
  • Anton J M de Craen
  • David J Stott
  • Brendan M Buckley
  • Ian Ford
  • Rudi G J Westendorp
  • P Eline Slagboom
  • Naveed Sattar
  • Patricia B Munroe
  • Peter Sever
  • Neil Poulter
  • Alice Stanton
  • Denis C Shields
  • Eoin O'Brien
  • Sue Shaw-Hawkins
  • Y-D Ida Chen
  • Deborah A Nickerson
  • Joshua D Smith
  • Marie Pierre Dubé
  • S Matthijs Boekholdt
  • G Kees Hovingh
  • John J P Kastelein
  • Paul M McKeigue
  • John Betteridge
  • Andrew Neil
  • Paul N Durrington
  • Alex Doney
  • Fiona Carr
  • Andrew Morris
  • Mark I McCarthy
  • Leif Groop
  • Emma Ahlqvist
  • Joshua C Bis
  • Kenneth Rice
  • Nicholas L Smith
  • Thomas Lumley
  • Eric A Whitsel
  • Til Stürmer
  • Eric Boerwinkle
  • Julius S Ngwa
  • Christopher J O'Donnell
  • Ramachandran S Vasan
  • Wei-Qi Wei
  • Russell A Wilke
  • Ching-Ti Liu
  • Fangui Sun
  • Xiuqing Guo
  • Susan R Heckbert
  • Wendy Post
  • Nona Sotoodehnia
  • Alice M Arnold
  • Jeanette M Stafford
  • Jingzhong Ding
  • David M Herrington
  • Stephen B Kritchevsky
  • Gudny Eiriksdottir
  • Leonore J Launer
  • Tamara B Harris
  • Audrey Y Chu
  • Franco Giulianini
  • Jean G MacFadyen
  • Bryan J Barratt
  • Fredrik Nyberg
  • Bruno H Stricker
  • André G Uitterlinden
  • Albert Hofman
  • Fernando Rivadeneira
  • Valur Emilsson
  • Oscar H Franco
  • Paul M Ridker
  • Vilmundur Gudnason
  • Yongmei Liu
  • Joshua C Denny
  • Christie M Ballantyne
  • Jerome I Rotter
  • L Adrienne Cupples
  • Bruce M Psaty
  • Colin N A Palmer
  • Jean-Claude Tardif
  • Helen M Colhoun
  • Graham Hitman
  • Ronald M Krauss
  • J Wouter Jukema
  • Mark J Caulfield
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Summary, in English

Statins effectively lower LDL cholesterol levels in large studies and the observed interindividual response variability may be partially explained by genetic variation. Here we perform a pharmacogenetic meta-analysis of genome-wide association studies (GWAS) in studies addressing the LDL cholesterol response to statins, including up to 18,596 statin-treated subjects. We validate the most promising signals in a further 22,318 statin recipients and identify two loci, SORT1/CELSR2/PSRC1 and SLCO1B1, not previously identified in GWAS. Moreover, we confirm the previously described associations with APOE and LPA. Our findings advance the understanding of the pharmacogenetic architecture of statin response.

Publishing year

2014

Language

English

Publication/Series

Nature Communications

Volume

5

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Endocrinology and Diabetes

Status

Published

Research group

  • Translational Muscle Research

ISBN/ISSN/Other

  • ISSN: 2041-1723