Meta-Analysis of Genome-Wide Association Studies of HDL Cholesterol Response to Statins

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Citation

Postmus, Iris; Warren, Helen R.; Trompet, Stella; Arsenault, Benoit J.; Avery, Christy L.; Bis, Joshua C.; Chasman, Daniel I.; de Keyser, Catherine E.; Deshmukh, Harshal A.; & Evans, Daniel S., et al. (2016). Meta-Analysis of Genome-Wide Association Studies of HDL Cholesterol Response to Statins. Journal of Medical Genetics, 53(12), 835-845. PMCID: PMC5309131

Abstract

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<1x10-4 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<5x10-8) 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.

URL

http://dx.doi.org/10.1136/jmedgenet-2016-103966

Reference Type

Journal Article

Year Published

2016

Journal Title

Journal of Medical Genetics

Author(s)

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

PMCID

PMC5309131

ORCiD

Avery - 0000-0002-1044-8162