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Meta-analysis of genome-wide association studies of HDL cholesterol response to statins.
Tuesday,2017-05-02 16:29 America/Los_Angeles — ecterry
| Title | Meta-analysis of genome-wide association studies of HDL cholesterol response to statins. |
| Publication Type | Journal Article |
| Year of Publication | 2016 |
| Authors | Postmus, 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, Stürmer, T, Uitterlinden, AG, Wei, W-Q, Westendorp, RGJ, Whitsel, EA, Wiggins, KL, Wilke, RA, Ballantyne, CM, Colhoun, HM, Cupples, AL, 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, Krauss, RM |
| Journal | J Med Genet |
| Volume | 53 |
| Issue | 12 |
| Pagination | 835-845 |
| Date Published | 2016 Dec |
| ISSN | 1468-6244 |
| Abstract | <p><b>BACKGROUND: </b>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.</p><p><b>METHODS AND RESULTS: </b>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<1×10(-4) from the 16 769 statin-treated participants in the first analysis stage were followed up in an independent group of 10 951 statin-treated individuals, providing a total sample size of 27 720 individuals. The only associations of genome-wide significance (p<5×10(-8)) were between minor alleles at the CETP locus and greater HDL-C response to statin treatment.</p><p><b>CONCLUSIONS: </b>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.</p> |
| DOI | 10.1136/jmedgenet-2016-103966 |
| Alternate Journal | J. Med. Genet. |
| PubMed ID | 27587472 |
| PubMed Central ID | PMC5309131 |
| Grant List | 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 N01HC95160 / HL / NHLBI NIH HHS / United States R01 HL120393 / HL / NHLBI NIH HHS / United States HHSN268201100010C / HL / NHLBI NIH HHS / United States UL1 RR025005 / RR / NCRR NIH HHS / United States N01 AG062101 / AG / NIA NIH HHS / United States N01HC95163 / HL / NHLBI 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 R01 HL068986 / HL / NHLBI NIH HHS / United States R01 HL059367 / HL / NHLBI NIH HHS / United States HHSN268201100007C / HL / NHLBI NIH HHS / United States HHSN268200800007C / HL / NHLBI NIH HHS / United States R01 HL085251 / HL / NHLBI NIH HHS / United States N01HC95169 / HL / NHLBI NIH HHS / United States Z01 AG007380-02 / / Intramural NIH HHS / United States HHSN268201100011I / HL / NHLBI 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 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 N01 AG062106 / AG / NIA NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States N01HC95162 / HL / NHLBI NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States R01 HL105756 / HL / NHLBI NIH HHS / United States N01HC95168 / HL / NHLBI NIH HHS / United States R01 AG032098 / AG / NIA 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 HHSN268201200036C / HL / NHLBI NIH HHS / United States HHSN268201100005I / HL / NHLBI NIH HHS / United States N01 AG062103 / AG / NIA NIH HHS / United States N01HC95165 / HL / NHLBI NIH HHS / United States N01HC95161 / HL / NHLBI NIH HHS / United States P50 GM115305 / GM / NIGMS NIH HHS / United States N01HC85082 / HL / NHLBI NIH HHS / United States N01HC95167 / HL / NHLBI NIH HHS / United States R01 HL043201 / 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 N01HC85083 / HL / NHLBI NIH HHS / United States HHSN268201100005C / HL / NHLBI NIH HHS / United States N01HC25195 / HL / NHLBI NIH HHS / United States HHSN268201100007I / HL / NHLBI NIH HHS / United States UL1 RR024975 / RR / NCRR NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States N01HC95166 / HL / NHLBI NIH HHS / United States R01 AG023629 / AG / NIA NIH HHS / United States R01 HL087641 / HL / NHLBI NIH HHS / United States R01 HL073410 / HL / NHLBI NIH HHS / United States P2C HD050924 / HD / NICHD NIH HHS / United States G0600237 / / Medical Research Council / United Kingdom N01HC85080 / HL / NHLBI NIH HHS / United States N01 HC095159 / HC / NHLBI NIH HHS / United States N01HC85081 / HL / NHLBI NIH HHS / United States |
ePub date:
16/12