Meta-analysis of genome-wide association studies of HDL cholesterol response to statins

Research output: Contribution to journalJournal articleResearchpeer-review

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

BACKGROUND: In addition to lowering low density lipoprotein cholesterol (LDL-C), statin therapy also raises high density lipoprotein cholesterol (HDL-C) levels. Inter-individual variation in HDL-C response to statins may be partially explained by genetic variation.

METHODS AND RESULTS: We performed a meta-analysis of genome-wide association studies (GWAS) to identify variants with an effect on statin-induced high density lipoprotein cholesterol (HDL-C) changes. The 123 most promising signals with p<1×10(-4) from the 16 769 statin-treated participants in the first analysis stage were followed up in an independent group of 10 951 statin-treated individuals, providing a total sample size of 27 720 individuals. The only associations of genome-wide significance (p<5×10(-8)) were between minor alleles at the CETP locus and greater HDL-C response to statin treatment.

CONCLUSIONS: Based on results from this study that included a relatively large sample size, we suggest that CETP may be the only detectable locus with common genetic variants that influence HDL-C response to statins substantially in individuals of European descent. Although CETP is known to be associated with HDL-C, we provide evidence that this pharmacogenetic effect is independent of its association with baseline HDL-C levels.

Original languageEnglish
JournalJournal of Medical Genetics
Issue number12
Pages (from-to)835-845
Number of pages11
Publication statusPublished - Dec 2016

ID: 166326259