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

2019-11-22T16:24:14Z (GMT) by 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 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 Dubé 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 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 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 André 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

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.