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

Author

Listed:
  • Iris Postmus

    (Leiden University Medical Center
    The Netherlands Consortium for Healthy Ageing)

  • Stella Trompet

    (Leiden University Medical Center
    Leiden University Medical Center)

  • Harshal A. Deshmukh

    (Medical Research Institute, Ninewells Hospital and Medical School, University of Dundee)

  • Michael R. Barnes

    (Genome Centre, William Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London
    NIHR Barts Cardiovascular Biomedical Research Unit, Queen Mary University of London)

  • Xiaohui Li

    (Institute for Translational Genomics and Population Sciences, Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center)

  • Helen R. Warren

    (NIHR Barts Cardiovascular Biomedical Research Unit, Queen Mary University of London
    William Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London)

  • Daniel I. Chasman

    (Brigham and Women's Hospital
    Harvard Medical School)

  • Kaixin Zhou

    (Medical Research Institute, Ninewells Hospital and Medical School, University of Dundee)

  • Benoit J. Arsenault

    (Montreal Heart Institute, Universite de Montreal)

  • Louise A. Donnelly

    (Medical Research Institute, Ninewells Hospital and Medical School, University of Dundee)

  • Kerri L. Wiggins

    (Cardiovascular Health Research Unit, University of Washington)

  • Christy L. Avery

    (University of North Carolina)

  • Paula Griffin

    (Boston University School of Public Health)

  • QiPing Feng

    (Vanderbilt University)

  • Kent D. Taylor

    (Institute for Translational Genomics and Population Sciences, Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center)

  • Guo Li

    (Cardiovascular Health Research Unit, University of Washington)

  • Daniel S. Evans

    (California Pacific Medical Center Research Institute)

  • Albert V. Smith

    (Icelandic Heart Association
    University of Iceland)

  • Catherine E. de Keyser

    (Erasmus Medical Center
    Health Care Inspectorate)

  • Andrew D. Johnson

    (Framingham Heart Study (FHS) of the National Heart, Lung and Blood Institute, Cardiovascular Epidemiology and Human Genomics)

  • Anton J. M. de Craen

    (Leiden University Medical Center
    The Netherlands Consortium for Healthy Ageing)

  • David J. Stott

    (Faculty of Medicine, Institute of Cardiovascular and Medical Sciences, University of Glasgow)

  • Brendan M. Buckley

    (University College Cork)

  • Ian Ford

    (Robertson Center for Biostatistics, University of Glasgow)

  • Rudi G. J. Westendorp

    (Leiden University Medical Center
    The Netherlands Consortium for Healthy Ageing
    Leyden Academy of Vitality and Ageing)

  • P. Eline Slagboom

    (The Netherlands Consortium for Healthy Ageing
    Leiden University Medical Center)

  • Naveed Sattar

    (Faculty of Medicine, BHF Glasgow Cardiovascular Research Centre)

  • Patricia B. Munroe

    (NIHR Barts Cardiovascular Biomedical Research Unit, Queen Mary University of London
    William Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London)

  • Peter Sever

    (International Centre for Circulatory Health, Imperial College)

  • Neil Poulter

    (International Centre for Circulatory Health, Imperial College)

  • Alice Stanton

    (Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland
    Beaumont Hospital)

  • Denis C. Shields

    (The Conway Institute, University College Dublin
    School of Medicine and Medical Sciences, University College Dublin)

  • Eoin O’Brien

    (The Conway Institute, University College Dublin)

  • Sue Shaw-Hawkins

    (Genome Centre, William Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London
    NIHR Barts Cardiovascular Biomedical Research Unit, Queen Mary University of London)

  • Y.-D. Ida Chen

    (Institute for Translational Genomics and Population Sciences, Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center)

  • Deborah A. Nickerson

    (University of Washington)

  • Joshua D. Smith

    (University of Washington)

  • Marie Pierre Dubé

    (Montreal Heart Institute, Universite de Montreal)

  • S. Matthijs Boekholdt

    (Academic Medical Center)

  • G. Kees Hovingh

    (Academic Medical Center)

  • John J. P. Kastelein

    (Academic Medical Center)

  • Paul M. McKeigue

    (University of Edinburgh)

  • John Betteridge
  • Andrew Neil

    (University of Oxford)

  • Paul N. Durrington

    (Cardiovascular Research Group, School of Biosciences, University of Manchester)

  • Alex Doney

    (Medical Research Institute, Ninewells Hospital and Medical School, University of Dundee)

  • Fiona Carr

    (Medical Research Institute, Ninewells Hospital and Medical School, University of Dundee)

  • Andrew Morris

    (Medical Research Institute, Ninewells Hospital and Medical School, University of Dundee)

  • Mark I. McCarthy

    (Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Old Road
    Wellcome Trust Centre for Human Genetics, University of Oxford
    Oxford NIHR Biomedical Research Centre, Churchill Hospital, Old Road)

  • Leif Groop

    (Lund University)

  • Emma Ahlqvist

    (Lund University)

  • Joshua C. Bis

    (Cardiovascular Health Research Unit, University of Washington)

  • Kenneth Rice

    (University of Washington)

  • Nicholas L. Smith

    (University of Washington
    Group Health Research Institute, Group Health Cooperative
    Seattle Epidemiologic Research and Information Center)

  • Thomas Lumley

    (Cardiovascular Health Research Unit, University of Washington
    University of Auckland)

  • Eric A. Whitsel

    (University of North Carolina
    University of North Carolina)

  • Til Stürmer

    (University of North Carolina)

  • Eric Boerwinkle

    (Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston)

  • Julius S. Ngwa

    (Boston University School of Public Health)

  • Christopher J. O’Donnell

    (NHLBI Framingham Heart Study
    Massachusetts General Hospital, Harvard Medical School
    National Heart, Lung and Blood Institute)

  • Ramachandran S. Vasan

    (Section of Preventive Medicine and Epidemiology, Boston University School of Medicine, and the Framingham Heart Study)

  • Wei-Qi Wei

    (Vanderbilt University)

  • Russell A. Wilke

    (Center for IMAGENETICS, Sanford Healthcare)

  • Ching-Ti Liu

    (Boston University School of Public Health)

  • Fangui Sun

    (Boston University School of Public Health)

  • Xiuqing Guo

    (Institute for Translational Genomics and Population Sciences, Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center)

  • Susan R Heckbert

    (University of Washington
    Group Health Research Institute, Group Health Cooperative
    Cardiovascular Health Research Unit, University of Washington)

  • Wendy Post

    (Johns Hopkins University)

  • Nona Sotoodehnia

    (Cardiovascular Health Research Unit, University of Washington
    Harborview Medical Center, University of Washington)

  • Alice M. Arnold

    (University of Washington)

  • Jeanette M. Stafford

    (Wake Forest School of Medicine)

  • Jingzhong Ding

    (Wake Forest School of Medicine)

  • David M. Herrington

    (Section on Cardiology, Wake Forest School of Medicine)

  • Stephen B. Kritchevsky

    (Wake Forest School of Medicine)

  • Gudny Eiriksdottir

    (Icelandic Heart Association)

  • Leonore J. Launer

    (Laboratory of Epidemiology, Demography, Biometry, National Institute on Aging, National Institutes of Health)

  • Tamara B. Harris

    (Laboratory of Epidemiology, Demography, Biometry, National Institute on Aging, National Institutes of Health)

  • Audrey Y. Chu

    (Brigham and Women's Hospital)

  • Franco Giulianini

    (Brigham and Women's Hospital)

  • Jean G. MacFadyen

    (Brigham and Women's Hospital)

  • Bryan J. Barratt

    (Personalised Healthcare and Biomarkers, AstraZeneca)

  • Fredrik Nyberg

    (AstraZeneca Research and Development
    Unit of Occupational and Environmental Medicine, University of Gothenburg)

  • Bruno H. Stricker

    (Erasmus Medical Center
    Health Care Inspectorate
    Erasmus Medical Center)

  • André G. Uitterlinden

    (The Netherlands Consortium for Healthy Ageing
    Erasmus Medical Center
    Erasmus Medical Center)

  • Albert Hofman

    (The Netherlands Consortium for Healthy Ageing
    Erasmus Medical Center)

  • Fernando Rivadeneira

    (Erasmus Medical Center)

  • Valur Emilsson

    (Icelandic Heart Association)

  • Oscar H. Franco

    (Erasmus Medical Center)

  • Paul M. Ridker

    (Brigham and Women's Hospital)

  • Vilmundur Gudnason

    (Icelandic Heart Association
    University of Iceland)

  • Yongmei Liu

    (Wake Forest School of Medicine)

  • Joshua C. Denny

    (Vanderbilt University
    Vanderbilt University)

  • Christie M. Ballantyne

    (Baylor College of Medicine)

  • Jerome I. Rotter

    (Institute for Translational Genomics and Population Sciences, Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center)

  • L. Adrienne Cupples

    (Boston University School of Public Health
    NHLBI Framingham Heart Study)

  • Bruce M. Psaty

    (Cardiovascular Health Research Unit, University of Washington
    University of Washington
    Group Health Research Institute, Group Health Cooperative
    University of Washington)

  • Colin N. A. Palmer

    (Medical Research Institute, Ninewells Hospital and Medical School, University of Dundee)

  • Jean-Claude Tardif

    (Montreal Heart Institute, Universite de Montreal)

  • Helen M. Colhoun

    (Medical Research Institute, Ninewells Hospital and Medical School, University of Dundee
    University of Dundee)

  • Graham Hitman

    (Barts and the London School of Medicine and Dentistry, Queen Mary University of London)

  • Ronald M. Krauss

    (Children’s Hospital Oakland Research Institute)

  • J Wouter Jukema

    (Leiden University Medical Center
    Durrer Center for Cardiogenetic Research
    Interuniversity Cardiology Institute of the Netherlands)

  • Mark J. Caulfield

    (NIHR Barts Cardiovascular Biomedical Research Unit, Queen Mary University of London
    William Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London)

Abstract

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.

Suggested Citation

  • Iris Postmus & Stella Trompet & Harshal A. Deshmukh & Michael R. Barnes & Xiaohui Li & Helen R. Warren & Daniel I. Chasman & Kaixin Zhou & Benoit J. Arsenault & Louise A. Donnelly & Kerri L. Wiggins &, 2014. "Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins," Nature Communications, Nature, vol. 5(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6068
    DOI: 10.1038/ncomms6068
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    Cited by:

    1. Samvida S. Venkatesh & Habib Ganjgahi & Duncan S. Palmer & Kayesha Coley & Gregorio V. Linchangco & Qin Hui & Peter Wilson & Yuk-Lam Ho & Kelly Cho & Kadri Arumäe & Laura B. L. Wittemans & Christoffer, 2024. "Characterising the genetic architecture of changes in adiposity during adulthood using electronic health records," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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