TY - JOUR T1 - Meta-analysis of genome-wide association studies of HDL cholesterol response to statins. JF - J Med Genet Y1 - 2016 A1 - Postmus, Iris A1 - Warren, Helen R A1 - Trompet, Stella A1 - Arsenault, Benoit J A1 - Avery, Christy L A1 - Bis, Joshua C A1 - Chasman, Daniel I A1 - de Keyser, Catherine E A1 - Deshmukh, Harshal A A1 - Evans, Daniel S A1 - Feng, QiPing A1 - Li, Xiaohui A1 - Smit, Roelof A J A1 - Smith, Albert V A1 - Sun, Fangui A1 - Taylor, Kent D A1 - Arnold, Alice M A1 - Barnes, Michael R A1 - Barratt, Bryan J A1 - Betteridge, John A1 - Boekholdt, S Matthijs A1 - Boerwinkle, Eric A1 - Buckley, Brendan M A1 - Chen, Y-D Ida A1 - de Craen, Anton J M A1 - Cummings, Steven R A1 - Denny, Joshua C A1 - Dubé, Marie Pierre A1 - Durrington, Paul N A1 - Eiriksdottir, Gudny A1 - Ford, Ian A1 - Guo, Xiuqing A1 - Harris, Tamara B A1 - Heckbert, Susan R A1 - Hofman, Albert A1 - Hovingh, G Kees A1 - Kastelein, John J P A1 - Launer, Leonore J A1 - Liu, Ching-Ti A1 - Liu, Yongmei A1 - Lumley, Thomas A1 - McKeigue, Paul M A1 - Munroe, Patricia B A1 - Neil, Andrew A1 - Nickerson, Deborah A A1 - Nyberg, Fredrik A1 - O'Brien, Eoin A1 - O'Donnell, Christopher J A1 - Post, Wendy A1 - Poulter, Neil A1 - Vasan, Ramachandran S A1 - Rice, Kenneth A1 - Rich, Stephen S A1 - Rivadeneira, Fernando A1 - Sattar, Naveed A1 - Sever, Peter A1 - Shaw-Hawkins, Sue A1 - Shields, Denis C A1 - Slagboom, P Eline A1 - Smith, Nicholas L A1 - Smith, Joshua D A1 - Sotoodehnia, Nona A1 - Stanton, Alice A1 - Stott, David J A1 - Stricker, Bruno H A1 - Stürmer, Til A1 - Uitterlinden, André G A1 - Wei, Wei-Qi A1 - Westendorp, Rudi G J A1 - Whitsel, Eric A A1 - Wiggins, Kerri L A1 - Wilke, Russell A A1 - Ballantyne, Christie M A1 - Colhoun, Helen M A1 - Cupples, L Adrienne A1 - Franco, Oscar H A1 - Gudnason, Vilmundur A1 - Hitman, Graham A1 - Palmer, Colin N A A1 - Psaty, Bruce M A1 - Ridker, Paul M A1 - Stafford, Jeanette M A1 - Stein, Charles M A1 - Tardif, Jean-Claude A1 - Caulfield, Mark J A1 - Jukema, J Wouter A1 - Rotter, Jerome I A1 - Krauss, Ronald M AB -

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.

VL - 53 IS - 12 ER -