Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins
Nature Communications2014Vol. 5(1), pp. 5068–5068
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Iris Postmus, Stella Trompet, Harshal Deshmukh, Michael R. Barnes, Xiaohui Li, Helen R. Warren, Daniel I. Chasman, Kaixin Zhou, Benoît J. Arsenault, Louise A. Donnelly, Kerri L. Wiggins, Christy L. Avery, Paula J. Griffin, QiPing Feng, Kent D. Taylor, Guo Li, Daniel S. Evans, Albert V. Smith, Catherine E. de Keyser, Andrew D. Johnson, 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 OʼBrien, Sue Shaw‐Hawkins, Yu Chen, Deborah A. Nickerson, Joshua D. Smith, Marie‐Pierre Dubé, S. Matthijs Boekholdt, G. Kees Hovingh, John J.P. Kastelein, Paul McKeigue, John Betteridge, Andrew Neil, Paul N. Durrington, Alex S. F. Doney, Fiona Carr, Andrew P. Morris, Mark I. McCarthy, Leif Groop, Emma Ahlqvist, Joshua C. Bis, Kenneth Rice, Nicholas L. Smith, Thomas Lumley, Eric A. Whitsel, Til Stürmer, 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 S. Post, Nona Sotoodehnia, Alice M. Arnold, Jeanette M. Stafford, Jingzhong Ding, David M. Herrington, Stephen B. Kritchevsky, Guðný Eiríksdóttir, Leonore J. Launer, Tamara B. Harris, Audrey Y. Chu, Franco Giulianini, Jean MacFadyen, Bryan J. Barratt, Fredrik Nyberg, Bruno H. Stricker, André G. Uitterlinden, Albert Hofman, Fernando Rivadeneira, Valur Emilsson, Oscar H. Franco, Paul M. Ridker, Vilmundur Guðnason, Ching‐Ti 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, G. A. Hitman, Ronald M. Krauss, J. Wouter Jukema, Mark J. Caulfield, Peter Donnelly, Inês 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 Sawcer, Richard C. Trembath, Ananth C. Viswanathan, Nicholas Wood, Data and Analysis Group, Chris C. A. Spencer, Gavin Band, Céline Bellenguez, Colin L. Freeman, Garrett Hellenthal, Eleni Giannoulatou, Matti Pirinen, Richard D. Pearson, Amy Strange, Zhan Su, Damjan Vukcevic, Peter Donnelly, DNA, Genotyping, Data QC and Informatics Group, Cordelia Langford, Sarah 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 Potter, Rathi Ravindrarajah, Michelle Ricketts, Matthew Waller, Paul A. 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
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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