title: Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins.
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.
authors.affiliation: 1] Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden 2300 RC, The Netherlands [2] The Netherlands Consortium for Healthy Ageing, Leiden 2300 RC, The Netherlands.
authors.forename: Iris
authors.initials: I
authors.lastname: Postmus
authors.affiliation: 1] Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden 2300 RC, The Netherlands [2] Department of Cardiology, Leiden University Medical Center, Leiden 2300 RC, The Netherlands.
authors.forename: Stella
authors.initials: S
authors.lastname: Trompet
authors.affiliation: Medical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, UK.
authors.forename: Harshal A
authors.initials: HA
authors.lastname: Deshmukh
authors.affiliation: 1] Genome Centre, William Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London, London EC1M6BQ, UK [2] NIHR Barts Cardiovascular Biomedical Research Unit, Queen Mary University of London, London EC1M 6BQ, UK.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Barnes
authors.affiliation: Institute for Translational Genomics and Population Sciences, Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center, Torrance, California 90502, USA.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Li
authors.affiliation: 1] NIHR Barts Cardiovascular Biomedical Research Unit, Queen Mary University of London, London EC1M 6BQ, UK [2] Department of Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London, London EC1M6BQ, UK.
authors.forename: Helen R
authors.initials: HR
authors.lastname: Warren
authors.affiliation: 1] Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02215-1204, USA [2] Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Chasman
authors.affiliation: Medical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, UK.
authors.forename: Kaixin
authors.initials: K
authors.lastname: Zhou
authors.affiliation: Montreal Heart Institute, Universite de Montreal, Montreal H1T 1C8, Quebec, Canada.
authors.forename: Benoit J
authors.initials: BJ
authors.lastname: Arsenault
authors.affiliation: Medical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, UK.
authors.forename: Louise A
authors.initials: LA
authors.lastname: Donnelly
authors.affiliation: Cardiovascular Health Research Unit, Department of Medicine, University of Washington, 98101 Seattle, Washington, USA.
authors.forename: Kerri L
authors.initials: KL
authors.lastname: Wiggins
authors.affiliation: Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
authors.forename: Christy L
authors.initials: CL
authors.lastname: Avery
authors.affiliation: Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts 02215, USA.
authors.forename: Paula
authors.initials: P
authors.lastname: Griffin
authors.affiliation: Department of Clinical Pharmacology, Vanderbilt University, Nashville, Tennessee 37240, USA.
authors.forename: QiPing
authors.initials: Q
authors.lastname: Feng
authors.affiliation: Institute for Translational Genomics and Population Sciences, Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center, Torrance, California 90502, USA.
authors.forename: Kent D
authors.initials: KD
authors.lastname: Taylor
authors.affiliation: Cardiovascular Health Research Unit, Department of Medicine, University of Washington, 98101 Seattle, Washington, USA.
authors.forename: Guo
authors.initials: G
authors.lastname: Li
authors.affiliation: California Pacific Medical Center Research Institute, San Francisco, California 94107, USA.
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authors.initials: DS
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authors.affiliation: 1] Icelandic Heart Association, IS-201 Kopavogur, Iceland [2] University of Iceland, IS-101 Reykjavik, Iceland.
authors.forename: Albert V
authors.initials: AV
authors.lastname: Smith
authors.affiliation: 1] Department of Epidemiology, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands [2] Health Care Inspectorate, 2595 AN The Hague, The Netherlands.
authors.forename: Catherine E
authors.initials: CE
authors.lastname: de Keyser
authors.affiliation: Framingham Heart Study (FHS) of the National Heart, Lung and Blood Institute, Cardiovascular Epidemiology and Human Genomics, Framingham, Massachusetts 01702, USA.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Johnson
authors.affiliation: 1] Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden 2300 RC, The Netherlands [2] The Netherlands Consortium for Healthy Ageing, Leiden 2300 RC, The Netherlands.
authors.forename: Anton J M
authors.initials: AJ
authors.lastname: de Craen
authors.affiliation: Faculty of Medicine, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow G31 2ER, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Stott
authors.affiliation: Department of Pharmacology and Therapeutics, University College Cork, Cork 30, Ireland.
authors.forename: Brendan M
authors.initials: BM
authors.lastname: Buckley
authors.affiliation: Robertson Center for Biostatistics, University of Glasgow, Glasgow G12 8QQ, UK.
authors.forename: Ian
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authors.lastname: Ford
authors.affiliation: 1] Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden 2300 RC, The Netherlands [2] The Netherlands Consortium for Healthy Ageing, Leiden 2300 RC, The Netherlands [3] Leyden Academy of Vitality and Ageing, 2333 AA Leiden, The Netherlands.
authors.forename: Rudi G J
authors.initials: RG
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authors.affiliation: 1] The Netherlands Consortium for Healthy Ageing, Leiden 2300 RC, The Netherlands [2] Department of Molecular Epidemiology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
authors.forename: P Eline
authors.initials: PE
authors.lastname: Slagboom
authors.affiliation: Faculty of Medicine, BHF Glasgow Cardiovascular Research Centre, Glasgow G12 8QQ, UK.
authors.forename: Naveed
authors.initials: N
authors.lastname: Sattar
authors.affiliation: 1] NIHR Barts Cardiovascular Biomedical Research Unit, Queen Mary University of London, London EC1M 6BQ, UK [2] Department of Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London, London EC1M6BQ, UK.
authors.forename: Patricia B
authors.initials: PB
authors.lastname: Munroe
authors.affiliation: International Centre for Circulatory Health, Imperial College, London SW7 2AZ, UK.
authors.forename: Peter
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authors.lastname: Sever
authors.affiliation: International Centre for Circulatory Health, Imperial College, London SW7 2AZ, UK.
authors.forename: Neil
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authors.forename: Alice
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authors.affiliation: 1] The Conway Institute, University College Dublin, Dublin 4, Ireland [2] School of Medicine and Medical Sciences, University College Dublin, Dublin 4, Ireland.
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authors.initials: DC
authors.lastname: Shields
authors.affiliation: The Conway Institute, University College Dublin, Dublin 4, Ireland.
authors.forename: Eoin
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authors.affiliation: 1] Genome Centre, William Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London, London EC1M6BQ, UK [2] NIHR Barts Cardiovascular Biomedical Research Unit, Queen Mary University of London, London EC1M 6BQ, UK.
authors.forename: Sue
authors.initials: S
authors.lastname: Shaw-Hawkins
authors.affiliation: Institute for Translational Genomics and Population Sciences, Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center, Torrance, California 90502, USA.
authors.forename: Y-D Ida
authors.initials: YD
authors.lastname: Chen
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, Washington 98101, USA.
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Nickerson
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, Washington 98101, USA.
authors.forename: Joshua D
authors.initials: JD
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authors.affiliation: Montreal Heart Institute, Universite de Montreal, Montreal H1T 1C8, Quebec, Canada.
authors.forename: Marie Pierre
authors.initials: MP
authors.lastname: Dubé
authors.affiliation: Department of Cardiology, Academic Medical Center, 1100 DD Amsterdam, The Netherlands.
authors.forename: S Matthijs
authors.initials: SM
authors.lastname: Boekholdt
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, 1100 DD Amsterdam, The Netherlands.
authors.forename: G Kees
authors.initials: GK
authors.lastname: Hovingh
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, 1100 DD Amsterdam, The Netherlands.
authors.forename: John J P
authors.initials: JJ
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authors.affiliation: University of Edinburgh, Edinburgh EH9 3JR, UK.
authors.forename: Paul M
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authors.forename: John
authors.initials: J
authors.lastname: Betteridge
authors.affiliation: University of Oxford, Oxford OX1 2JD, UK.
authors.forename: Andrew
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authors.affiliation: Cardiovascular Research Group, School of Biosciences, University of Manchester, Manchester M13 9NT, UK.
authors.forename: Paul N
authors.initials: PN
authors.lastname: Durrington
authors.affiliation: Medical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, UK.
authors.forename: Alex
authors.initials: A
authors.lastname: Doney
authors.affiliation: Medical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, UK.
authors.forename: Fiona
authors.initials: F
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authors.affiliation: Medical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, UK.
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authors.lastname: Morris
authors.affiliation: 1] Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Old Road, Headington, Oxford OX3 7LJ, UK [2] Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK [3] Oxford NIHR Biomedical Research Centre, Churchill Hospital, Old Road, Headington, Oxford OX3 7LJ, UK.
authors.forename: Mark I
authors.initials: MI
authors.lastname: McCarthy
authors.affiliation: Department of Clinical Sciences/Diabetes &Endocrinology, Lund University, Malmo 205 02, Sweden.
authors.forename: Leif
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authors.lastname: Groop
authors.affiliation: Department of Clinical Sciences/Diabetes &Endocrinology, Lund University, Malmo 205 02, Sweden.
authors.forename: Emma
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authors.affiliation: Cardiovascular Health Research Unit, Department of Medicine, University of Washington, 98101 Seattle, Washington, USA.
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authors.affiliation: Department of Biostatistics, University of Washington, 98115 Seattle, Washington, USA.
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authors.affiliation: 1] Department of Epidemiology, University of Washington, Seattle, Washington 98195, USA [2] Group Health Research Institute, Group Health Cooperative, Seattle, Washington 98101, USA [3] Seattle Epidemiologic Research and Information Center, Department of Veterans Affairs Office of Research and Development, Seattle, Washington 98101, USA.
authors.forename: Nicholas L
authors.initials: NL
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authors.affiliation: 1] Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina 27599, USA [2] Department of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Whitsel
authors.affiliation: Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
authors.forename: Til
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authors.lastname: Stürmer
authors.affiliation: Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, Texas 77030, USA.
authors.forename: Eric
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authors.lastname: Boerwinkle
authors.affiliation: Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts 02215, USA.
authors.forename: Julius S
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authors.affiliation: 1] NHLBI Framingham Heart Study, Framingham, Massachusetts 01701, USA [2] Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA [3] National Heart, Lung and Blood Institute, Bethesda, Maryland 20892, USA.
authors.forename: Christopher J
authors.initials: CJ
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authors.affiliation: Section of Preventive Medicine and Epidemiology, Department of Medicine, Boston University School of Medicine, and the Framingham Heart Study, Framingham, Massachusetts 01701, USA.
authors.forename: Ramachandran S
authors.initials: RS
authors.lastname: Vasan
authors.affiliation: Department of Biomedical Informatics, Vanderbilt University, Nashville, Tennessee 37240, USA.
authors.forename: Wei-Qi
authors.initials: WQ
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authors.affiliation: Department of Internal Medicine, Center for IMAGENETICS, Sanford Healthcare, Fargo, North Dakota, 58104 USA.
authors.forename: Russell A
authors.initials: RA
authors.lastname: Wilke
authors.affiliation: Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts 02215, USA.
authors.forename: Ching-Ti
authors.initials: CT
authors.lastname: Liu
authors.affiliation: Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts 02215, USA.
authors.forename: Fangui
authors.initials: F
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authors.affiliation: Institute for Translational Genomics and Population Sciences, Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center, Torrance, California 90502, USA.
authors.forename: Xiuqing
authors.initials: X
authors.lastname: Guo
authors.affiliation: 1] Department of Epidemiology, University of Washington, Seattle, Washington 98195, USA [2] Group Health Research Institute, Group Health Cooperative, Seattle, Washington 98101, USA [3] Cardiovascular Health Research Unit, University of Washington, Seattle, Washington 98101, USA.
authors.forename: Susan R
authors.initials: SR
authors.lastname: Heckbert
authors.affiliation: Department of Cardiology, Johns Hopkins University, Baltimore, Maryland 21218, USA.
authors.forename: Wendy
authors.initials: W
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authors.affiliation: 1] Cardiovascular Health Research Unit, Department of Medicine, University of Washington, 98101 Seattle, Washington, USA [2] Division of Cardiology, Harborview Medical Center, University of Washington, Seattle 98101, Washington, USA.
authors.forename: Nona
authors.initials: N
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authors.affiliation: Department of Biostatistics, University of Washington, 98115 Seattle, Washington, USA.
authors.forename: Alice M
authors.initials: AM
authors.lastname: Arnold
authors.affiliation: Division of Public Health Sciences, Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157, USA.
authors.forename: Jeanette M
authors.initials: JM
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authors.affiliation: Division of Public Health Sciences, Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157, USA.
authors.forename: Jingzhong
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authors.affiliation: Department of Internal Medicine, Section on Cardiology, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157, USA.
authors.forename: David M
authors.initials: DM
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authors.affiliation: Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157, USA.
authors.forename: Stephen B
authors.initials: SB
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authors.affiliation: Icelandic Heart Association, IS-201 Kopavogur, Iceland.
authors.forename: Gudny
authors.initials: G
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authors.affiliation: Laboratory of Epidemiology, Demography, Biometry, National Institute on Aging, National Institutes of Health, 7201 Wisconsin Avenue, Bethesda, Maryland 20892, USA.
authors.forename: Leonore J
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authors.affiliation: Laboratory of Epidemiology, Demography, Biometry, National Institute on Aging, National Institutes of Health, 7201 Wisconsin Avenue, Bethesda, Maryland 20892, USA.
authors.forename: Tamara B
authors.initials: TB
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authors.affiliation: Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02215-1204, USA.
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authors.initials: AY
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authors.affiliation: Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02215-1204, USA.
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authors.initials: F
authors.lastname: Giulianini
authors.affiliation: Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02215-1204, USA.
authors.forename: Jean G
authors.initials: JG
authors.lastname: MacFadyen
authors.affiliation: Personalised Healthcare and Biomarkers, AstraZeneca, Alderley Park SK10 4TG, UK.
authors.forename: Bryan J
authors.initials: BJ
authors.lastname: Barratt
authors.affiliation: 1] AstraZeneca Research and Development, 481 83 Mölndal, Sweden [2] Unit of Occupational and Environmental Medicine, University of Gothenburg, 405 30 Gothenburg, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Nyberg
authors.affiliation: 1] Department of Epidemiology, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands [2] Health Care Inspectorate, 2595 AN The Hague, The Netherlands [3] Department of Internal Medicine, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands.
authors.forename: Bruno H
authors.initials: BH
authors.lastname: Stricker
authors.affiliation: 1] The Netherlands Consortium for Healthy Ageing, Leiden 2300 RC, The Netherlands [2] Department of Epidemiology, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands [3] Department of Internal Medicine, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands.
authors.forename: André G
authors.initials: AG
authors.lastname: Uitterlinden
authors.affiliation: 1] The Netherlands Consortium for Healthy Ageing, Leiden 2300 RC, The Netherlands [2] Department of Epidemiology, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands.
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.affiliation: Department of Internal Medicine, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands.
authors.forename: Fernando
authors.initials: F
authors.lastname: Rivadeneira
authors.affiliation: Icelandic Heart Association, IS-201 Kopavogur, Iceland.
authors.forename: Valur
authors.initials: V
authors.lastname: Emilsson
authors.affiliation: Department of Epidemiology, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands.
authors.forename: Oscar H
authors.initials: OH
authors.lastname: Franco
authors.affiliation: Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02215-1204, USA.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Ridker
authors.affiliation: 1] Icelandic Heart Association, IS-201 Kopavogur, Iceland [2] University of Iceland, IS-101 Reykjavik, Iceland.
authors.forename: Vilmundur
authors.initials: V
authors.lastname: Gudnason
authors.affiliation: Division of Public Health Sciences, Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157, USA.
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Liu
authors.affiliation: 1] Department of Biomedical Informatics, Vanderbilt University, Nashville, Tennessee 37240, USA [2] Department of Medicine, Vanderbilt University, Vanderbilt, Tennessee 37240, USA.
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Denny
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Christie M
authors.initials: CM
authors.lastname: Ballantyne
authors.affiliation: Institute for Translational Genomics and Population Sciences, Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center, Torrance, California 90502, USA.
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.affiliation: 1] Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts 02215, USA [2] NHLBI Framingham Heart Study, Framingham, Massachusetts 01701, USA.
authors.forename: L
authors.initials: L
authors.lastname: Adrienne Cupples
authors.affiliation: 1] Cardiovascular Health Research Unit, Department of Medicine, University of Washington, 98101 Seattle, Washington, USA [2] Department of Epidemiology, University of Washington, Seattle, Washington 98195, USA [3] Group Health Research Institute, Group Health Cooperative, Seattle, Washington 98101, USA [4] Department of Health Services, University of Washington, Seattle, Washington 98101, USA.
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Psaty
authors.affiliation: Medical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, UK.
authors.forename: Colin N A
authors.initials: CN
authors.lastname: Palmer
authors.affiliation: Montreal Heart Institute, Universite de Montreal, Montreal H1T 1C8, Quebec, Canada.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Tardif
authors.affiliation: 1] Medical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, UK [2] Department of Public Health, University of Dundee, Dundee DD1 9SY, UK.
authors.forename: Helen M
authors.initials: HM
authors.lastname: Colhoun
authors.affiliation: Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK.
authors.forename: Graham
authors.initials: G
authors.lastname: Hitman
authors.affiliation: Children's Hospital Oakland Research Institute, Oakland, California 94609, USA.
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Krauss
authors.affiliation: 1] Department of Cardiology, Leiden University Medical Center, Leiden 2300 RC, The Netherlands [2] Durrer Center for Cardiogenetic Research, 1105 AZ Amsterdam, The Netherlands [3] Interuniversity Cardiology Institute of the Netherlands, 3511 GC Utrecht, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Wouter Jukema
authors.affiliation: 1] NIHR Barts Cardiovascular Biomedical Research Unit, Queen Mary University of London, London EC1M 6BQ, UK [2] Department of Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London, London EC1M6BQ, UK.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Caulfield
mesh_terms: D008078:Cholesterol, LDL / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
chemical_list: D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors