4.8 Article

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

期刊

NATURE COMMUNICATIONS
卷 5, 期 -, 页码 -

出版社

NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms6068

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资金

  1. Bristol-Myers Squibb, USA
  2. European Union [HEALTH-F2-2009-223004]
  3. Netherlands Consortium for Healthy Ageing (NGI) [05060810]
  4. Pfizer, USA
  5. National Institutes for Health Research (NIHR) as part of the portfolio of translational research of the NIHR Biomedical Research Unit at Barts
  6. NIHR Biomedical Research Centre at Imperial College
  7. International Centre for Circulatory Health Charity
  8. Medical Research Council [G952010]
  9. Pfizer, Diabetes UK
  10. Department of Health
  11. National Institutes of Health from the National Heart, Lung, and Blood Institute [U19 HL069757]
  12. National Center for Advancing Translational Sciences [UL1TR000124, 2 UL1 TR000445]
  13. Pfizer
  14. NIH [N01-AG-1-2100]
  15. NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association)
  16. Althingi (the Icelandic Parliament)
  17. National Heart, Lung, and Blood Institute contracts [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, R01HL087641, R01HL59367, R01HL086694]
  18. National Human Genome Research Institute contract [U01HG004402]
  19. National Institutes of Health contract [HHSN268200625226C]
  20. National Institutes of Health and NIH Roadmap for Medical Research [UL1RR025005]
  21. National Center for Research Resources [UL1 RR024975]
  22. National Human Genome Research Institute [U01-HG04603]
  23. National Insitute of General Medical Sciences [RC2-GM092318]
  24. NHLBI [HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, HL080295, N01HC85086, HL087652, HL105756, HL103612, HL085251, HL073410, HL068986]
  25. National Institute of Neurological Disorders and Stroke (NINDS)
  26. National Institute on Aging (NIA) [AG023629]
  27. National Center for Advancing Translational Sciences
  28. CTSI grant [UL1TR000124]
  29. National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) grant [DK063491]
  30. National Heart Lung and Blood Institute of the National Institutes of Health
  31. Boston University School of Medicine [N01-HC-25195]
  32. Affymetrix, Inc. [N02-HL-6-4278]
  33. Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine
  34. Boston Medical Center [R01HL103612]
  35. Wellcome Trust United Kingdom Type 2 Diabetes Case Control Collection (GoDARTS)
  36. Scottish Health Informatics Programme
  37. Wellcome Trust Case Control Consortium
  38. Diabetes UK [07/0003525]
  39. Wellcome Trust [084727/Z/08/Z, 085475/Z/08/Z, 085475/B/08/Z]
  40. EU IMI-SUMMIT programme
  41. NIA [N01AG62101, N01AG62103, N01AG62106, 1R01AG032098-01A1]
  42. National Institutes of Health [HHSN268200782096C]
  43. Intramural Research Program of the NIH, National Institute on Aging
  44. National Heart, Lung, and Blood Institute (NHLBI)
  45. MESA investigators
  46. Clinical Translational Science Institute grant [UL1RR033176]
  47. AstraZeneca
  48. Erasmus Medical Center
  49. Erasmus University Rotterdam
  50. Netherlands Organization for Health Research and Development (ZonMw)
  51. Research Institute for Diseases in the Elderly
  52. Ministry of Education, Culture and Science
  53. Ministry of Health Welfare and Sports
  54. European Commission
  55. Municipality of Rotterdam
  56. Netherlands Genomics Initiative (NGI) Netherlands Organization for Scietific Research (NOW) [050-060-810]
  57. [N01 HC-95159]
  58. [N01-HC-95169]
  59. [RR024156]
  60. MRC [G0400126, G9521010] Funding Source: UKRI
  61. British Heart Foundation [PG/13/66/30442] Funding Source: researchfish
  62. Medical Research Council [MR/K006584/1, G0400126, G9521010] Funding Source: researchfish
  63. National Institute for Health Research [NF-SI-0513-10059, NF-SI-0512-10113] Funding Source: researchfish

向作者/读者索取更多资源

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.

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