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

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, Qi Ping 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 BetteridgeS. 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, Paul M. McKeigue, Thomas Lumley, Patricia B. Munroe, Andrew Neil, Deborah A. Nickerson, Fredrik Nyberg, Eoin O'Brien, Christopher J. O'Donnell, Wendy S 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, Rudi G J Westendorp, 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

Research output: Contribution to journalArticle

Abstract

Background In addition to lowering low density lipoprotein cholesterol (LDL-C), statin therapy also raises high density lipoprotein cholesterol (HDL-C) levels. Interindividual 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 statintreated individuals, providing a total sample size of 27 720 individuals. The only associations of genomewide 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 (US)
JournalJournal of Medical Genetics
DOIs
Publication statusAccepted/In press - Sep 1 2016

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ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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Postmus, I., Warren, H. R., Trompet, S., Arsenault, B. J., Avery, C. L., Bis, J. C., ... Krauss, R. M. (Accepted/In press). Meta-analysis of genome-wide association studies of HDL cholesterol response to statins. Journal of Medical Genetics. https://doi.org/10.1136/jmedgenet-2016-103966