title: A genetic risk score is associated with statin-induced low-density lipoprotein cholesterol lowering.
abstract: To find new genetic loci associated with statin response, and to investigate the association of a genetic risk score (GRS) with this outcome.
  
  
  
  In a discovery meta-analysis (five studies, 1991 individuals), we investigated the effects of approximately 50000 single nucleotide polymorphisms on statin response, following up associations with p < 1 × 10(-4) (three independent studies, 5314 individuals). We further assessed the effect of a GRS based on SNPs in ABCG2, LPA and APOE.
  
  
  
  No new SNPs were found associated with statin response. The GRS was associated with reduced statin response: 0.0394 mmol/l per allele (95% CI: 0.0171-0.0617, p = 5.37 × 10(-4)).
  
  
  
  The GRS was associated with statin response, but the small effect size (˜2% of the average low-density lipoprotein cholesterol reduction) limits applicability.
authors.affiliation: Division of Pharmacoepidemiology & Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands.|Julius Center for Health Sciences & Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Maarten
authors.initials: M
authors.lastname: Leusink
authors.affiliation: Division of Pharmacoepidemiology & Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands.
authors.forename: Anke H
authors.initials: AH
authors.lastname: Maitland-van der Zee
authors.affiliation: Medical Evidence & Observational Research Center, Global Medical Affairs, AstraZeneca R&D Gothenburg, Mölndal, Sweden.
authors.forename: Bo
authors.initials: B
authors.lastname: Ding
authors.affiliation: Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, London, UK.|MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
authors.forename: Fotios
authors.initials: F
authors.lastname: Drenos
authors.affiliation: Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, The Netherlands.|Department of Clinical Epidemiology, Biostatistics & Bioinformatics, Academic Medical Center Amsterdam, Amsterdam, The Netherlands.
authors.forename: Erik Pa
authors.initials: EP
authors.lastname: van Iperen
authors.affiliation: Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.|NIHR Barts Cardiovascular Biomedical Research Unit, Queen Mary University of London, London, UK.
authors.forename: Helen R
authors.initials: HR
authors.lastname: Warren
authors.affiliation: Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.|NIHR Barts Cardiovascular Biomedical Research Unit, Queen Mary University of London, London, UK.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Caulfield
authors.affiliation: Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.|The National Heart, Lung, & Blood Institute Framingham Heart Study, Framingham, MA, USA.
authors.forename: L Adrienne
authors.initials: LA
authors.lastname: Cupples
authors.affiliation: Departments of Medicine & Pathology, University of Vermont, Burlington, VT, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Cushman
authors.affiliation: Department of Epidemiology & Public Health, UCL Institute of Epidemiology & Health Care, University College London, London, UK.
authors.forename: Aroon D
authors.initials: AD
authors.lastname: Hingorani
authors.affiliation: Division of Atherosclerosis & Vascular Medicine, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Ron C
authors.initials: RC
authors.lastname: Hoogeveen
authors.affiliation: Department of Vascular Medicine, Academic Medical Center Amsterdam, Amsterdam, The Netherlands.
authors.forename: G Kees
authors.initials: GK
authors.lastname: Hovingh
authors.affiliation: Department of Epidemiology & Public Health, UCL Institute of Epidemiology & Health Care, University College London, London, UK.
authors.forename: Meena
authors.initials: M
authors.lastname: Kumari
authors.affiliation: Department of Genetics, University of North Carolina School of Medicine at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Lange
authors.affiliation: Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.|NIHR Barts Cardiovascular Biomedical Research Unit, Queen Mary University of London, London, UK.
authors.forename: Patricia B
authors.initials: PB
authors.lastname: Munroe
authors.affiliation: Medical Evidence & Observational Research Center, Global Medical Affairs, AstraZeneca R&D Gothenburg, Mölndal, Sweden.|Occupational & Environmental Medicine, Department of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Nyberg
authors.affiliation: School of Public Health, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Schreiner
authors.affiliation: Department of Vascular Medicine, Academic Medical Center Amsterdam, Amsterdam, The Netherlands.
authors.forename: Suthesh
authors.initials: S
authors.lastname: Sivapalaratnam
authors.affiliation: Julius Center for Health Sciences & Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.|Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Paul Iw
authors.initials: PI
authors.lastname: de Bakker
authors.affiliation: Division of Pharmacoepidemiology & Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands.
authors.forename: Anthonius
authors.initials: A
authors.lastname: de Boer
authors.affiliation: Division of Transplantation, Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Brendan J
authors.initials: BJ
authors.lastname: Keating
authors.affiliation: Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, The Netherlands.|Department of Cardiology, Division Heart & Lungs, University Medical Center Utrecht, Utrecht, The Netherlands.|Faculty of Population Health Sciences, Institute of Cardiovascular Science, University College London, London, UK.
authors.forename: Folkert W
authors.initials: FW
authors.lastname: Asselbergs
authors.affiliation: Julius Center for Health Sciences & Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: N Charlotte
authors.initials: NC
authors.lastname: Onland-Moret
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2 / Q000235:genetics; D000328:Adult; D000368:Aged; D001057:Apolipoproteins E / Q000235:genetics; D008078:Cholesterol, LDL / Q000097:blood* / Q000235:genetics*; D005260:Female; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors
chemical_list: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D001057:Apolipoproteins E; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors
keywords: pharmacogenetics cholesterol; risk score; statin therapy