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

Wednesday,2015-03-04 14:00 America/Los_Angeles — zdrager
TitlePharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins.
Publication TypeJournal Article
Year of Publication2014
AuthorsPostmus, 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, QP, Taylor, KD, Li, G, Evans, DS, Smith, AV, de Keyser, CE, Johnson, AD, de Craen, AJM, Stott, DJ, Buckley, BM, Ford, I, Westendorp, RGJ, P Slagboom, E, Sattar, N, Munroe, PB, Sever, P, Poulter, N, Stanton, A, Shields, DC, O'Brien, E, Shaw-Hawkins, S, Chen, Y-DIda, Nickerson, DA, Smith, JD, Dubé, MPierre, S Boekholdt, M, G Hovingh, K, Kastelein, JJP, McKeigue, PM, Betteridge, J, Neil, A, Durrington, PN, Doney, A, Carr, F, Morris, A, McCarthy, MI, Groop, L, Ahlqvist, E, 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, L Cupples, A, Psaty, BM, Palmer, CNA, Tardif, J-C, Colhoun, HM, Hitman, G, Krauss, RM, J Jukema, W, Caulfield, MJ
Corporate/Institutional AuthorsWelcome Trust Case Control Consortium
JournalNat Commun
Volume5
Pagination5068
Date Published2014 Oct 28
ISSN2041-1723
KeywordsCholesterol, LDL, Genome-Wide Association Study, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Pharmacogenetics, Polymorphism, Single Nucleotide
Abstract<p>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. </p>
DOI10.1038/ncomms6068
Alternate JournalNat Commun
PubMed ID25350695
PubMed Central IDPMC4220464
Grant ListHHSN268201100012C / HL / NHLBI NIH HHS / United States
N01 HC-95169 / HC / NHLBI NIH HHS / United States
N01HC55222 / HC / NHLBI NIH HHS / United States
UL1RR025005 / RR / NCRR NIH HHS / United States
N02-HL-6-4278 / HL / NHLBI NIH HHS / United States
N01-HC-25195 / HC / NHLBI NIH HHS / United States
HL073410 / HL / NHLBI NIH HHS / United States
UL1 RR033176 / RR / NCRR NIH HHS / United States
G9521010 / / Medical Research Council / United Kingdom
R01 HL103612 / HL / NHLBI NIH HHS / United States
HHSN268201100009I / HL / NHLBI NIH HHS / United States
UL1 TR000445 / TR / NCATS NIH HHS / United States
084727/Z/08/Z / / Wellcome Trust / United Kingdom
UL1RR033176 / RR / NCRR NIH HHS / United States
UL1TR000124 / TR / NCATS NIH HHS / United States
N01 HC-95165 / HC / NHLBI NIH HHS / United States
PG/13/66/30442 / / British Heart Foundation / United Kingdom
R01HL59367 / HL / NHLBI NIH HHS / United States
HHSN268201100010C / HL / NHLBI NIH HHS / United States
N01HC85080 / HC / NHLBI NIH HHS / United States
UL1 RR025005 / RR / NCRR NIH HHS / United States
N01 AG062101 / AG / NIA NIH HHS / United States
HHSN268201100008C / HL / NHLBI NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
HHSN268201100005G / HL / NHLBI NIH HHS / United States
HHSN268201100008I / HL / NHLBI NIH HHS / United States
HL085251 / HL / NHLBI NIH HHS / United States
U01-HG04603 / HG / NHGRI NIH HHS / United States
HHSN268201100005C / / PHS HHS / United States
R01 HL068986 / HL / NHLBI NIH HHS / United States
R01 HL059367 / HL / NHLBI NIH HHS / United States
HHSN268201100007C / HL / NHLBI NIH HHS / United States
HL105756 / HL / NHLBI NIH HHS / United States
RR-024156 / RR / NCRR NIH HHS / United States
HHSN268200800007C / HL / NHLBI NIH HHS / United States
R01 HL085251 / HL / NHLBI NIH HHS / United States
U19 HL065962 / HL / NHLBI NIH HHS / United States
N01HC95169 / HL / NHLBI NIH HHS / United States
2 UL1 TR000445 / TR / NCATS NIH HHS / United States
N01 HC-95168 / HC / NHLBI NIH HHS / United States
HHSN268201100009C / / PHS HHS / United States
HHSN268201100011I / HL / NHLBI NIH HHS / United States
P30 DK079637 / DK / NIDDK NIH HHS / United States
HHSN268201100011C / HL / NHLBI NIH HHS / United States
R01 HL086694 / HL / NHLBI NIH HHS / United States
U01 HG004603 / HG / NHGRI NIH HHS / United States
UL1 RR024156 / RR / NCRR NIH HHS / United States
N01 HC-95164 / HC / NHLBI NIH HHS / United States
1R01AG032098-01A1 / AG / NIA NIH HHS / United States
/ / Department of Health / United Kingdom
R01 HL087652 / HL / NHLBI NIH HHS / United States
HHSN268200625226C / / PHS HHS / United States
U01 HG004402 / HG / NHGRI NIH HHS / United States
N01-AG-1-2100 / AG / NIA NIH HHS / United States
HL087652 / HL / NHLBI NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
N01 AG062106 / AG / NIA NIH HHS / United States
N01HC55222 / HL / NHLBI NIH HHS / United States
HL068986 / HL / NHLBI NIH HHS / United States
N01 HC-95160 / HC / NHLBI NIH HHS / United States
HHSN268201100010C / / PHS HHS / United States
N01HC85086 / HL / NHLBI NIH HHS / United States
R01 HL105756 / HL / NHLBI NIH HHS / United States
U01HG004402 / HG / NHGRI NIH HHS / United States
R01 AG032098 / AG / NIA NIH HHS / United States
N01HC85081 / HC / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
HHSN268200782096C / HG / NHGRI NIH HHS / United States
HHSN268201100006C / HL / NHLBI NIH HHS / United States
/ / Intramural NIH HHS / United States
N01HC85079 / HC / NHLBI NIH HHS / United States
HHSN268201200036C / HL / NHLBI NIH HHS / United States
HHSN268201100008C / / PHS HHS / United States
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HHSN268201100012C / / PHS HHS / United States
R01HL087641 / HL / NHLBI NIH HHS / United States
N01 HC-95159 / HC / NHLBI NIH HHS / United States
HHSN268201100005I / HL / NHLBI NIH HHS / United States
N01 AG062103 / AG / NIA NIH HHS / United States
RC2-GM092318 / GM / NIGMS NIH HHS / United States
N01HC85086 / HC / NHLBI NIH HHS / United States
N01 HC-95161 / HC / NHLBI NIH HHS / United States
R01 HL080295 / HL / NHLBI NIH HHS / United States
085475/B/08/Z / / Wellcome Trust / United Kingdom
N01HC85082 / HC / NHLBI NIH HHS / United States
HHSN268201100007C / / PHS HHS / United States
G952010 / / Medical Research Council / United Kingdom
N01 HC-95163 / HC / NHLBI NIH HHS / United States
HHSN268200800007C / / PHS HHS / United States
N01HC85082 / HL / NHLBI NIH HHS / United States
U19 HL069757 / HL / NHLBI NIH HHS / United States
MR/K006584/1 / / Medical Research Council / United Kingdom
HHSN268201100009C / HL / NHLBI NIH HHS / United States
HHSN268201100011C / / PHS HHS / United States
N01HC85083 / HL / NHLBI NIH HHS / United States
HHSN268201100005C / HL / NHLBI NIH HHS / United States
N01HC25195 / HL / NHLBI NIH HHS / United States
N01 HC-95166 / HC / NHLBI NIH HHS / United States
DK063491 / DK / NIDDK NIH HHS / United States
HHSN268201100007I / HL / NHLBI NIH HHS / United States
UL1 RR024975 / RR / NCRR NIH HHS / United States
HHSN268201200036C / / PHS HHS / United States
HHSN268200782096C / / PHS HHS / United States
HL080295 / HL / NHLBI NIH HHS / United States
N01HC85083 / HC / NHLBI NIH HHS / United States
R01HL103612 / HL / NHLBI NIH HHS / United States
N01HC85079 / HL / NHLBI NIH HHS / United States
HHSN268201100006C / / PHS HHS / United States
R01 AG023629 / AG / NIA NIH HHS / United States
R01 HL087641 / HL / NHLBI NIH HHS / United States
HL103612 / HL / NHLBI NIH HHS / United States
R01 HL073410 / HL / NHLBI NIH HHS / United States
N01HC85080 / HL / NHLBI NIH HHS / United States
AG023629 / AG / NIA NIH HHS / United States
R56 AG023629 / AG / NIA NIH HHS / United States
N01 HC-95162 / HC / NHLBI NIH HHS / United States
085475/Z/08/Z / / Wellcome Trust / United Kingdom
N01 HC095159 / HC / NHLBI NIH HHS / United States
N01HC85081 / HL / NHLBI NIH HHS / United States
R01HL086694 / HL / NHLBI NIH HHS / United States

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