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

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Iris Postmus, Stella Trompet, Harshal A. Deshmukh, Michael R. Barnes, Xiaohui Li, Helen R. Warren, Daniel I. Chasman, Kaixin Zhou, Benoit J. Arsenault, Louise A. Donnelly, Kerri L. Wiggins, Christy L. Avery, Paula Griffin, Qiping Feng, Kent D. Taylor, Guo Li, Daniel S. Evans, Albert V. Smith, Catherine E. De Keyser, Andrew D. Johnson & 142 more Anton J. M. De Craen, David J. Stott, Brendan M. Buckley, Ian Ford, Rudi G. J. Westendorp, P. Eline Slagboom, Naveed Sattar, Patricia B. Munroe, Peter Sever, Neil Poulter, Alice Stanton, Denis C. Shields, Eoin O???brien, Sue Shaw-hawkins, Y.-d. Ida Chen, Deborah A. Nickerson, Joshua D. Smith, Marie Pierre Dub??, S. Matthijs Boekholdt, G. Kees Hovingh, John J. P. Kastelein, Paul M. Mckeigue, John Betteridge, Andrew Neil, Paul N. Durrington, Alex Doney, Fiona Carr, Andrew Morris, Mark I. Mccarthy, Leif Groop, Emma Ahlqvist, Joshua C. Bis, Kenneth Rice, Nicholas L. Smith, Thomas Lumley, Eric A. Whitsel, Til St??rmer, Eric Boerwinkle, Julius S. Ngwa, Christopher J. O???donnell, Ramachandran S. Vasan, Wei-qi Wei, Russell A. Wilke, Ching-ti Liu, Fangui Sun, Xiuqing Guo, Susan R Heckbert, Wendy Post, Nona Sotoodehnia, Alice M. Arnold, Jeanette M. Stafford, Jingzhong Ding, David M. Herrington, Stephen B. Kritchevsky, Gudny Eiriksdottir, Leonore J. Launer, Tamara B. Harris, Audrey Y. Chu, Franco Giulianini, Jean G. Macfadyen, Bryan J. Barratt, Fredrik Nyberg, Bruno H. Stricker, Andr?? G. Uitterlinden, Albert Hofman, Fernando Rivadeneira, Valur Emilsson, Oscar H. Franco, Paul M. Ridker, Vilmundur Gudnason, Yongmei Liu, Joshua C. Denny, Christie M. Ballantyne, Jerome I. Rotter, L. Adrienne Cupples, Bruce M. Psaty, Colin N. A. Palmer, Jean-claude Tardif, Helen M. Colhoun, Graham Hitman, Ronald M. Krauss, J Wouter Jukema, Mark J. Caulfield, Peter Donnelly, Ines Barroso, Jenefer M. Blackwell, Elvira Bramon, Matthew A. Brown, Juan P. Casas, Aiden Corvin, Panos Deloukas, Audrey Duncanson, Janusz Jankowski, Hugh S. Markus, Christopher G. Mathew, Colin N. A. Palmer, Robert Plomin, Anna Rautanen, Stephen J. Sawcer, Richard Trembath, Ananth C. Viswanathan, Nicholas W. Wood, Chris C. A. Spencer, Gavin Band, C??line Bellenguez, Colin Freeman, Garrett Hellenthal, Eleni Giannoulatou, Matti Pirinen, Richard Pearson, Amy Strange, Zhan Su, Damjan Vukcevic, Peter Donnelly, Cordelia Langford, Sarah E. Hunt, Sarah Edkins, Rhian Gwilliam, Hannah Blackburn, Suzannah J. Bumpstead, Serge Dronov, Matthew Gillman, Emma Gray, Naomi Hammond, Alagurevathi Jayakumar, Owen T. Mccann, Jennifer Liddle, Simon C. Potter, Radhi Ravindrarajah, Michelle Ricketts, Matthew Waller, Paul Weston, Sara Widaa, Pamela Whittaker, Ines Barroso, Panos Deloukas, Christopher G. Mathew, Jenefer M. Blackwell, Matthew A. Brown, Aiden Corvin, Mark I. Mccarthy, Chris C. A. Spencer

Original languageEnglish
Article number5068
JournalNature Communications
Volume5
DOIs
Publication statusPublished - 28 Oct 2014

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Abstract

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.

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