期刊
JOURNAL OF MEDICAL GENETICS
卷 53, 期 12, 页码 835-+出版社
BMJ PUBLISHING GROUP
DOI: 10.1136/jmedgenet-2016-103966
关键词
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资金
- Bristol-Myers Squibb, USA
- European Union [HEALTH-F2-2009-223004]
- Netherlands Consortium for Healthy Ageing [NGI: 05060810]
- Pfizer USA
- National Institutes for Health Research (NIHR)
- NIHR Biomedical Research Centre at Imperial College
- International Centre for Circulatory Health Charity
- Medical Research Council [G952010]
- Pfizer
- Diabetes UK [07/0003525]
- Department of Health
- National Institutes of Health from the National Heart, Lung, and Blood Institute [U19 HL069757]
- National Center for Advancing Translational Sciences [UL1TR000124, 2 UL1 TR000445]
- NIH [N01-AG-1-2100]
- NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association)
- Althingi (the Icelandic Parliament)
- National Heart, Lung and Blood Institute [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, R01HL087641, R01HL59367, R01HL086694]
- National Human Genome Research Institute [U01HG004402, U01-HG04603]
- National Institutes of Health [HHSN268200625226C, UL1RR025005, HHSN268200782096C]
- NIH Roadmap for Medical Research
- National Center for Research Resources [UL1 RR024975]
- National Institute of General Medical Sciences [RC2-GM092318]
- NHLBI [HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, U01HL080295, R01HL087652, R01HL105756, R01HL103612, R01HL120393, HL085251, HL073410, HL068986]
- National Institute on Aging (NIA) [R01AG023629]
- National Center for Advancing Translational Sciences, CTSI [UL1TR000124]
- National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) [DK063491]
- National Heart Lung and Blood Institute of the National Institutes of Health
- Boston University School of Medicine [N01-HC-25195]
- Affymetrix, Inc [N02-HL-6-4278]
- Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine
- Boston Medical Center
- NIA [N01AG62101, N01AG62103, N01AG62106, 1R01AG032098-01A1]
- Intramural Research Program of the NIH, National Institute on Aging
- National Heart, Lung and Blood Institute (NHLBI)
- Clinical Translational Science Institute [UL1RR033176]
- Erasmus Medical Center
- Erasmus University Rotterdam
- Netherlands Organization for Health Research and Development (ZonMw)
- Research Institute for Diseases in the Elderly
- Ministry of Education, Culture and Science
- Ministry of Health Welfare and Sports
- European Commission
- Municipality of Rotterdam
- Netherlands Genomics Initiative (NGI) Netherlands Organization for Scientific Research (NOW) [050-060-810]
- AstraZeneca
- Wellcome Trust [084727/Z/08/Z, 085475/Z/08/Z, 085475/B/08/Z]
- EU IMI-SUMMIT programme
- [N01 HC-95159]
- [N01-HC-95160]
- [N01-HC-95161]
- [N01-HC-95162]
- [N01-HC-95163]
- [N01-HC-95164]
- [N01-HC-95165]
- [N01-HC-95166]
- [N01-HC-95167]
- [N01-HC-95168]
- [N01-HC-95169]
- [RR-024156]
- Medical Research Council [MR/K006584/1, G0600237] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0513-10059, NF-SI-0512-10113] Funding Source: researchfish
- MRC [G0600237] Funding Source: UKRI
Background In addition to lowering low density lipoprotein cholesterol (LDL-C), statin therapy also raises high density lipoprotein cholesterol (HDL-C) levels. Interindividual 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<1x10(-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<5x10(-8)) were between minor alleles at the CETP locus and greater HDL-C response to statin treatment. 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.
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