Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins.
Postmus I., Trompet S., Deshmukh HA., Barnes MR., Li X., Warren HR., Chasman DI., Zhou K., Arsenault BJ., Donnelly LA., Wiggins KL., Avery CL., Griffin P., Feng Q., Taylor KD., Li G., Evans DS., Smith AV., de Keyser CE., Johnson AD., de Craen AJM., Stott DJ., Buckley BM., Ford I., Westendorp RGJ., Slagboom PE., Sattar N., Munroe PB., Sever P., Poulter N., Stanton A., Shields DC., O'Brien E., Shaw-Hawkins S., Chen Y-DI., Nickerson DA., Smith JD., Dubé MP., Boekholdt SM., Hovingh GK., Kastelein JJP., McKeigue PM., Betteridge J., Neil A., Durrington PN., Doney A., Carr F., Morris A., McCarthy MI., Groop L., Ahlqvist E., Welcome Trust Case Control Consortium None., Bis JC., Rice K., Smith NL., Lumley T., Whitsel EA., Stürmer T., Boerwinkle E., Ngwa JS., O'Donnell CJ., Vasan RS., Wei W-Q., Wilke RA., Liu C-T., Sun F., Guo X., Heckbert SR., Post W., Sotoodehnia N., Arnold AM., Stafford JM., Ding J., Herrington DM., Kritchevsky SB., Eiriksdottir G., Launer LJ., Harris TB., Chu AY., Giulianini F., MacFadyen JG., Barratt BJ., Nyberg F., Stricker BH., Uitterlinden AG., Hofman A., Rivadeneira F., Emilsson V., Franco OH., Ridker PM., Gudnason V., Liu Y., Denny JC., Ballantyne CM., Rotter JI., Adrienne Cupples L., Psaty BM., Palmer CNA., Tardif J-C., Colhoun HM., Hitman G., Krauss RM., Wouter Jukema J., Caulfield MJ.
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.