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

Postmus, Iris; Trompet, Stella; Deshmukh, Harshal A.; Li, Xiaohui; Warren, Helen R.; Chasman, Daniel I.; Donnelly, Louise A.; Zhou, Kaixin; Wiggins, Kerri L.; Feng, QiPing; Smith, Av; de Keyser, Catherine E.; Taylor, Kent D.; Li, Guo; de Craen, Anton J. M.; De Keyser, C. E.; Evans, Daniel S.; Griffin, Paula; De Craen, A. J. M.; Johnson, Andrew D.; Stott, David J.; Smith, Albert V.; Buckley, Brendan M.; Ford, Ian; Smith, Joshua D.; Westendorp, Rudi G. J.; Eline Slagboom, P.; Sattar, Naveed; Munroe, Patricia B.; Sever, Peter; Slagboom, Pe E.; Poulter, Neil; Ha, Deshmukh; Stanton, Alice; Shields, Denis C.; O’Brien, Eoin; Shaw-Hawkins, Sue; Ida Chen, Y.-D.; Barnes, Michael R.; Nickerson, Deborah A.; Pierre Dubé, Marie; Matthijs Boekholdt, S.; Arsenault, Benoit J.; Kees Hovingh, G.; Dubé,; Kastelein, John J. P.; Chen, Yd; Avery, Christy L.; McKeigue, Paul M.; Mr, Barnes; Neil, Andrew; Durrington, Paul N.; Doney, Alex; Hovingh, Gk K.; Carr, Fiona; Morris, Andrew; McCarthy, Mark I.; Groop, Leif; Smith, Nicholas L.; PierreDube, Marie; Dub,; KeesHovingh, G.; Rice, Kenneth; Hr, Warren; Di, Chasman; 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.; Betteridge, John; Post, Wendy; Sotoodehnia, Nona; Stafford, Jeanette M.; Ahlqvist, Emma; Ding, Jingzhong; Stu¨rmer, Til; Bis, Joshua C.; Herrington, David M.; Kritchevsky, Stephen B.; Eiriksdottir, Gudny; Palmer, Colin N. A.; Launer, Leonore J.; Harris, Tamara B.; Chu, Audrey Y.; Giulianini, Franco; Bramon, Elvira; MacFadyen, Jean G.; Brown, Matthew A.; Casas, Juan P.; Corvin, Aiden; Donnelly, Peter; Nyberg, Fredrik; Deloukas, Panos; Stricker, Bruno H.; Duncanson, Audrey; Arnold, Alice M.; Uitterlinden, André G.; Jankowski, Janusz; Hofman, Albert; Markus, Hugh S.; Rivadeneira, Fernando; Smith, N. L.; Emilsson, Valur; Mathew, Christopher G.; Franco, Oscar H.; Plomin, Robert; Ridker, Paul M.; Wouter Jukema, J.; Rautanen, Anna; Gudnason, Vilmundur; Sawcer, Stephen J.; Liu, Yongmei; Trembath, Richard C.; Barratt, Bryan J.; Denny, Joshua C.; Viswanathan, Ananth C.; Wood, Nicholas W.; Rotter, Jerome I.; Spencer, Chris C. A.; Psaty, Bruce M.; Tardif, Jean-Claude; Freeman, Colin; Colhoun, Helen M.; Hellenthal, Garrett; Hitman, Graham; Ballantyne, Christie M.; Adrienne Cupples, L.; Krauss, Ronald M.; Giannoulatou, Eleni; Pirinen, Matti; Caulfield, Mark J.; Pearson, Richard; La, Donnelly; Strange, Amy; Barroso, Ines; Su, Zhan; Blackwell, Jenefer M.; Vukcevic, Damjan; Langford, Cordelia; Hunt, Sarah E.; Edkins, Sarah; Gwilliam, Rhian; Bumpstead, Suzannah J.; Dronov, Serge; Band, Gavin; Gillman, Matthew; Bellenguez, Céline; Gray, Emma; Hammond, Naomi; Jayakumar, Alagurevathi; McCann, Owen T.; Liddle, Jennifer; Potter, Simon C.; Ravindrarajah, Radhi; Ricketts, Michelle; Kl, Wiggins; Blackburn, Hannah; Waller, Matthew; Weston, Paul; Widaa, Sara; Whittaker, Pamela; Cupples, L. A.; Cl, Avery; Consortium, Welcome Trust Case Control; Jukema, J. W.; Mj, Caulfield; Bj, Arsenault; Boekholdt, Sm Matthijs

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

Journal article published in 2014 by Iris Postmus, Stella Trompet, Harshal A. Deshmukh, Xiaohui Li, Helen R. Warren, Daniel I. Chasman, Louise A. Donnelly, Kaixin Zhou, Kerri L. Wiggins, QiPing Feng, Av Smith, Catherine E. de Keyser, Kent D. Taylor, Guo Li, Anton J. M. de Craen and other authors.

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

Abstract