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Meta-analysis of genome-wide association studies of HDL cholesterol response to statins.

TitleMeta-analysis of genome-wide association studies of HDL cholesterol response to statins.
Publication TypeJournal Article
Year of Publication2016
AuthorsPostmus I, Warren HR, Trompet S, Arsenault BJ, Avery CL, Bis JC, Chasman DI, de Keyser CE, Deshmukh HA, Evans DS, Feng QP, Li X, Smit RAJ, Smith AV, Sun F, Taylor KD, Arnold AM, Barnes MR, Barratt BJ, Betteridge J, S Boekholdt M, Boerwinkle E, Buckley BM, Chen Y-DIda, de Craen AJM, Cummings SR, Denny JC, Dubé MPierre, Durrington PN, Eiriksdottir G, Ford I, Guo X, Harris TB, Heckbert SR, Hofman A, G Hovingh K, Kastelein JJP, Launer LJ, Liu C-T, Liu Y, Lumley T, McKeigue PM, Munroe PB, Neil A, Nickerson DA, Nyberg F, O'Brien E, O'Donnell CJ, Post W, Poulter N, Vasan RS, Rice K, Rich SS, Rivadeneira F, Sattar N, Sever P, Shaw-Hawkins S, Shields DC, P Slagboom E, Smith NL, Smith JD, Sotoodehnia N, Stanton A, Stott DJ, Stricker BH, Sturmer T, Uitterlinden AG, Wei W-Q, Westendorp RGJ, Whitsel EA, Wiggins KL, Wilke RA, Ballantyne CM, Colhoun HM, L Cupples A, Franco OH, Gudnason V, Hitman G, Palmer CNA, Psaty BM, Ridker PM, Stafford JM, Stein CM, Tardif J-C, Caulfield MJ, J Jukema W, Rotter JI
Secondary AuthorsKrauss RM
JournalJ Med Genet
Volume53
Issue12
Pagination835-845
Date Published2016 12
ISSN1468-6244
KeywordsCholesterol Ester Transfer Proteins, Cholesterol, HDL, European Continental Ancestry Group, Female, Genome-Wide Association Study, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Male, Pharmacogenomic Variants, Polymorphism, Single Nucleotide, Treatment Outcome
Abstract

BACKGROUND: In addition to lowering low density lipoprotein cholesterol (LDL-C), statin therapy also raises high density lipoprotein cholesterol (HDL-C) levels. Inter-individual variation in HDL-C response to statins may be partially explained by genetic variation.

METHODS AND RESULTS: We performed a meta-analysis of genome-wide association studies (GWAS) to identify variants with an effect on statin-induced high density lipoprotein cholesterol (HDL-C) changes. The 123 most promising signals with p

CONCLUSIONS: Based on results from this study that included a relatively large sample size, we suggest that CETP may be the only detectable locus with common genetic variants that influence HDL-C response to statins substantially in individuals of European descent. Although CETP is known to be associated with HDL-C, we provide evidence that this pharmacogenetic effect is independent of its association with baseline HDL-C levels.
DOI10.1136/jmedgenet-2016-103966
Alternate JournalJ Med Genet
PubMed ID27587472
PubMed Central IDPMC5309131
Grant ListHHSN268201100010C / HL / NHLBI NIH HHS / United States
N01HC95161 / HL / NHLBI NIH HHS / United States
P50 GM115305 / GM / NIGMS NIH HHS / United States
HHSN268201100012C / HL / NHLBI NIH HHS / United States
UL1 RR033176 / RR / NCRR NIH HHS / United States
R01 HL103612 / HL / NHLBI NIH HHS / United States
HHSN268201100009I / HL / NHLBI NIH HHS / United States
UL1 TR000445 / TR / NCATS NIH HHS / United States
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UL1 RR025005 / RR / NCRR NIH HHS / United States
N01 AG062101 / AG / NIA NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
N01HC95163 / HL / NHLBI NIH HHS / United States
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HHSN268201100005G / HL / NHLBI NIH HHS / United States
HHSN268201100008I / HL / NHLBI NIH HHS / United States
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HHSN268201100007C / HL / NHLBI NIH HHS / United States
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Z01 AG007380-02 / / Intramural NIH HHS / United States
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HHSN268201100011C / HL / NHLBI NIH HHS / United States
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U01 HG004603 / HG / NHGRI NIH HHS / United States
/ DH_ / Department of Health / United Kingdom
UL1 RR024156 / RR / NCRR NIH HHS / United States
085475/B/08/Z / WT_ / Wellcome Trust / United Kingdom
R01 HL087652 / HL / NHLBI NIH HHS / United States
U01 HG004402 / HG / NHGRI NIH HHS / United States
N01HC95164 / HL / NHLBI NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
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084727/Z/08/Z / WT_ / Wellcome Trust / United Kingdom
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085475/Z/08/Z / WT_ / Wellcome Trust / United Kingdom
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MR/K006584/1 / / Medical Research Council / United Kingdom
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UL1 RR024975 / RR / NCRR NIH HHS / United States
/ / Wellcome Trust / United Kingdom
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R01 HL087641 / HL / NHLBI NIH HHS / United States
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P2C HD050924 / HD / NICHD NIH HHS / United States
G0600237 / / Medical Research Council / United Kingdom
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