Journal Article

Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins

Emilsson, Valur, Postmus, Iris, Ballantyne, Christie M., Psaty, Bruce M., Carr, Fiona, Gudnason, Vilmundur, Poulter, Neil, Betteridge, John, Caulfield, Mark J., MacFadyen, Jean G., Doney, Alex, Post, Wendy, Liu, Yongmei, Stanton, Alice, McKeigue, Paul M., Eiriksdottir, Gudny, Shaw-Hawkins, Sue, Barnes, Michael R., Smith, Joshua D., Palmer, Colin N. A., de Keyser, Catherine E., Munroe, Patricia B., O’Brien, Eoin, Liu, Ching-Ti, Durrington, Paul N., Zhou, Kaixin, Adrienne Cupples, L., Taylor, Kent D., Sever, Peter, Matthijs Boekholdt, S., Boerwinkle, Eric, Sotoodehnia, Nona, Wiggins, Kerri L., Buckley, Brendan M., Li, Xiaohui, Heckbert, Susan R, Sattar, Naveed, Krauss, Ronald M., Stott, David J., Ding, Jingzhong, Whitsel, Eric A., Uitterlinden, André G., Franco, Oscar H., Colhoun, Helen M., Donnelly, Louise A., Warren, Helen R., Deshmukh, Harshal A., Pierre Dubé, Marie, Smith, Albert V., Westendorp, Rudi G. J., Vasan, Ramachandran S., Tardif, Jean-Claude, Nyberg, Fredrik, Shields, Denis C., Feng, QiPing, Arnold, Alice M., Stürmer, Til, Arsenault, Benoit J., Trompet, Stella, Rivadeneira, Fernando, Sun, Fan

2014

Overview

Statins effectively lower LDL cholesterol levels in large studies and the observed interindividual response variability may be partially explained by genetic variation. Here we perform a pharmacogenetic meta-analysis of genome-wide association studies (GWAS) in studies addressing the LDL cholesterol response to statins, including up to 18,596 statin-treated subjects. We validate the most promising signals in a further 22,318 statin recipients and identify two loci, SORT1/CELSR2/PSRC1 and SLCO1B1 , not previously identified in GWAS. Moreover, we confirm the previously described associations with APOE and LPA. Our findings advance the understanding of the pharmacogenetic architecture of statin response. Statins are effectively used to prevent and manage cardiovascular disease, but patient response to these drugs is highly variable. Here, the authors identify two new genes associated with the response of LDL cholesterol to statins and advance our understanding of the genetic basis of drug response.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Pub. Group
• Subject: 45/43 / 631/208/726/649 / 631/92/436/434 / Cardiology and Cardiovascular Disease / Cholesterol / Cholesterol, LDL - genetics / Clinical Medicine / Endocrinology and Diabetes / Endokrinologi och diabetes / Farmakologi och toxikologi / Genetic diversity / Genome-Wide Association Study / Humanities and Social Sciences / Humans / Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology / Kardiologi och kardiovaskulära sjukdomar / Klinisk medicin / Medical and Health Sciences / Medicin och hälsovetenskap / multidisciplinary / Pharmacogenetics / Pharmacology and Toxicology / Polymorphism, Single Nucleotide - genetics / Science / Science (multidisciplinary) / Statins