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

药物遗传学荟萃分析：全基因组关联研究探讨他汀类药物对低密度脂蛋白胆固醇的影响

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作者：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,Slagboom,P Eline,Sattar,Naveed,Munroe,Patricia B,Sever,Peter,Poulter,Neil,Stanton,Alice,Shields,Denis C,O'Brien,Eoin,Shaw-Hawkins,Sue,Chen,Y-D Ida,Nickerson,Deborah A,Smith,Joshua D,Dubé,Marie Pierre,Boekholdt,S Matthijs,Hovingh,G Kees,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,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
期刊：Nature Communications影响因子：15.700
时间：2014起止号：2014 Oct 28;5:5068
doi：10.1038/ncomms6068研究方向： 代谢

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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