Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins
Authors: Postmus Iris , Trompet Stella , Deshmukh Harshal A. , Barnes Michael R. , Li Xiaohui , Warren Helen R. , Chasman Daniel I. , Zhou Kaixin , Arsenault Benoit J. , Donnelly Louise A. , Wiggins Kerri L. , Avery Christy L. , Griffin Paula , Feng QiPing , Taylor Kent D. , Li Guo , Evans Daniel S. , Smith Albert V. , de Keyser Catherine E. , Johnson Andrew D. , de Craen Anton J. M. , Stott David J. , Buckley Brendan M. , Ford Ian , Westendorp Rudi G. J. , Eline Slagboom P. , Sattar Naveed , Munroe Patricia B. , Sever Peter , Poulter Neil , Stanton Alice , Shields Denis C. , O’Brien Eoin , Shaw-Hawkins Sue , Ida Chen Y.-D. , Nickerson Deborah A. , Smith Joshua D. , Pierre Dubé Marie , Matthijs Boekholdt S. , Kees Hovingh G. , Kastelein John J. P. , McKeigue Paul M. , Betteridge John , Neil Andrew , Durrington Paul N. , Doney Alex , Carr Fiona , Morris Andrew , McCarthy Mark I. , Groop Leif , Ahlqvist Emma ,   Welcome Trust Case Control Consortium, Bis Joshua C. , Rice Kenneth , Smith Nicholas L. , Lumley Thomas , Whitsel Eric A. , Stürmer Til , Boerwinkle Eric , Ngwa Julius S. , O’Donnell Christopher J. , Vasan Ramachandran S. , Wei Wei-Qi , Wilke Russell A. , Liu Ching-Ti , Sun Fangui , Guo Xiuqing , Heckbert Susan R , Post Wendy , Sotoodehnia Nona , Arnold Alice M. , Stafford Jeanette M. , Ding Jingzhong , Herrington David M. , Kritchevsky Stephen B. , Eiriksdottir Gudny , Launer Leonore J. , Harris Tamara B. , Chu Audrey Y. , Giulianini Franco , MacFadyen Jean G. , Barratt Bryan J. , Nyberg Fredrik , Stricker Bruno H. , Uitterlinden André G. , Hofman Albert , Rivadeneira Fernando , Emilsson Valur , Franco Oscar H. , Ridker Paul M. , Gudnason Vilmundur , Liu Yongmei , Denny Joshua C. , Ballantyne Christie M. , Rotter Jerome I. , Adrienne Cupples L. , Psaty Bruce M. , Palmer Colin N. A. , Tardif Jean-Claude , Colhoun Helen M. , Hitman Graham , Krauss Ronald M. , Wouter Jukema J , Caulfield Mark J. ,   Membership of Wellcome Trust Case Control Consortium, Donnelly Peter , Barroso Ines , Blackwell Jenefer M. , Bramon Elvira , Brown Matthew A. , Casas Juan P. , Corvin Aiden , Deloukas Panos , Duncanson Audrey , Jankowski Janusz , Markus Hugh S. , Mathew Christopher G. , Palmer Colin N. A. , Plomin Robert , Rautanen Anna , Sawcer Stephen J. , Trembath Richard C. , Viswanathan Ananth C. , Wood Nicholas W. ,   Data and Analysis Group, Spencer Chris C. A. , Band Gavin , Bellenguez Céline , Freeman Colin , Hellenthal Garrett , Giannoulatou Eleni , Pirinen Matti , Pearson Richard , Strange Amy , Su Zhan , Vukcevic Damjan , Donnelly Peter ,   DNA, Genotyping, Data QC and Informatics Group, Langford Cordelia , Hunt Sarah E. , Edkins Sarah , Gwilliam Rhian , Blackburn Hannah , Bumpstead Suzannah J. , Dronov Serge , Gillman Matthew , Gray Emma , Hammond Naomi , Jayakumar Alagurevathi , McCann Owen T. , Liddle Jennifer , Potter Simon C. , Ravindrarajah Radhi , Ricketts Michelle , Waller Matthew , Weston Paul , Widaa Sara , Whittaker Pamela , Barroso Ines , Deloukas Panos ,   Publications Committee, Mathew Christopher G. , Blackwell Jenefer M. , Brown Matthew A. , Corvin Aiden , McCarthy Mark I. , Spencer Chris C. A. 
Published: October 2014

AbstractStatins 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.