%0 Journal Article %J J Med Genet %D 2016 %T Meta-analysis of genome-wide association studies of HDL cholesterol response to statins. %A Postmus, Iris %A Warren, Helen R %A Trompet, Stella %A Arsenault, Benoit J %A Avery, Christy L %A Bis, Joshua C %A Chasman, Daniel I %A de Keyser, Catherine E %A Deshmukh, Harshal A %A Evans, Daniel S %A Feng, QiPing %A Li, Xiaohui %A Smit, Roelof A J %A Smith, Albert V %A Sun, Fangui %A Taylor, Kent D %A Arnold, Alice M %A Barnes, Michael R %A Barratt, Bryan J %A Betteridge, John %A Boekholdt, S Matthijs %A Boerwinkle, Eric %A Buckley, Brendan M %A Chen, Y-D Ida %A de Craen, Anton J M %A Cummings, Steven R %A Denny, Joshua C %A Dubé, Marie Pierre %A Durrington, Paul N %A Eiriksdottir, Gudny %A Ford, Ian %A Guo, Xiuqing %A Harris, Tamara B %A Heckbert, Susan R %A Hofman, Albert %A Hovingh, G Kees %A Kastelein, John J P %A Launer, Leonore J %A Liu, Ching-Ti %A Liu, Yongmei %A Lumley, Thomas %A McKeigue, Paul M %A Munroe, Patricia B %A Neil, Andrew %A Nickerson, Deborah A %A Nyberg, Fredrik %A O'Brien, Eoin %A O'Donnell, Christopher J %A Post, Wendy %A Poulter, Neil %A Vasan, Ramachandran S %A Rice, Kenneth %A Rich, Stephen S %A Rivadeneira, Fernando %A Sattar, Naveed %A Sever, Peter %A Shaw-Hawkins, Sue %A Shields, Denis C %A Slagboom, P Eline %A Smith, Nicholas L %A Smith, Joshua D %A Sotoodehnia, Nona %A Stanton, Alice %A Stott, David J %A Stricker, Bruno H %A Stürmer, Til %A Uitterlinden, André G %A Wei, Wei-Qi %A Westendorp, Rudi G J %A Whitsel, Eric A %A Wiggins, Kerri L %A Wilke, Russell A %A Ballantyne, Christie M %A Colhoun, Helen M %A Cupples, L Adrienne %A Franco, Oscar H %A Gudnason, Vilmundur %A Hitman, Graham %A Palmer, Colin N A %A Psaty, Bruce M %A Ridker, Paul M %A Stafford, Jeanette M %A Stein, Charles M %A Tardif, Jean-Claude %A Caulfield, Mark J %A Jukema, J Wouter %A Rotter, Jerome I %A Krauss, Ronald M %X

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.

%B J Med Genet %V 53 %P 835-845 %8 2016 Dec %G eng %N 12 %R 10.1136/jmedgenet-2016-103966