title: Rooted in risk: genetic predisposition for low-density lipoprotein cholesterol level associates with diminished low-density lipoprotein cholesterol response to statin treatment.
abstract: To utilize previously reported lead SNPs for low-density lipoprotein cholesterol (LDL-c) levels to find additional loci of importance to statin response, and examine whether genetic predisposition to LDL-c levels associates with differential statin response.
  
  
  
  We investigated effects on statin response of 59 LDL-c SNPs, by combining summary level statistics from the Global Lipids Genetics and Genomic Investigation of Statin Therapy consortia.
  
  
  
  Lead SNPs for APOE, SORT1 and NPC1L1 were associated with a decreased LDL-c response to statin treatment, as was overall genetic predisposition for increased LDL-c levels as quantified with 59 SNPs, with a 5.4% smaller statin response per standard deviation increase in genetically raised LDL-c levels.
  
  
  
  Genetic predisposition for increased LDL-c level may decrease efficacy of statin therapy.
authors.affiliation: Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.|Section of Gerontology & Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Roelof Aj
authors.initials: RA
authors.lastname: Smit
authors.affiliation: Section of Gerontology & Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Iris
authors.initials: I
authors.lastname: Postmus
authors.affiliation: Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.|Section of Gerontology & Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Stella
authors.initials: S
authors.lastname: Trompet
authors.affiliation: William Harvey Research Institute, Barts & The London School of Medicine, Queen Mary University of London, London EC1M 6BQ, UK.|NIHR Barts Cardiovascular Biomedical Research Unit, Barts & The London School of Medicine, Queen Mary University of London, London EC1M 6BQ, UK.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Barnes
authors.affiliation: William Harvey Research Institute, Barts & The London School of Medicine, Queen Mary University of London, London EC1M 6BQ, UK.|NIHR Barts Cardiovascular Biomedical Research Unit, Barts & The London School of Medicine, Queen Mary University of London, London EC1M 6BQ, UK.
authors.forename: Helen
authors.initials: H
authors.lastname: Warren
authors.affiliation: Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Québec, Canada.
authors.forename: Benoit J
authors.initials: BJ
authors.lastname: Arsenault
authors.affiliation: Division of Preventive Medicine, Brigham & Women's Hospital, Boston, MA 02215, USA.|Harvard Medical School, Harvard University, Boston, MA 02115, USA.
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Chasman
authors.affiliation: Department of Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA.|National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA 01702-5827, USA.
authors.forename: L Adrienne
authors.initials: LA
authors.lastname: Cupples
authors.affiliation: Blizard Institute, Barts & The London School of Medicine & Dentistry, Queen Mary University of London, London EC1M 6BQ, UK.
authors.forename: Graham A
authors.initials: GA
authors.lastname: Hitman
authors.affiliation: Department of Atherosclerosis Research, Children's Hospital Oakland Research Institute, Oakland, CA 94609, USA.
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Krauss
authors.affiliation: Institute for Translational Genomics & Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Li
authors.affiliation: Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology & Health Services, University of Washington, Seattle, WA 98101, USA.|Group Health Research Institute, Group Health Cooperative, Seattle, WA 98101, USA.
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Psaty
authors.affiliation: Department of Medicine, Vanderbilt University, Nashville, TN 37232-6602, USA.|Department of Pharmacology, Vanderbilt University, Nashville, TN 37232-6602, USA.
authors.forename: Charles M
authors.initials: CM
authors.lastname: Stein
authors.affiliation: Institute for Translational Genomics & Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.affiliation: Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.|Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands.|Interuniversity Cardiology Institute Netherlands, Utrecht, The Netherlands.
authors.forename: J Wouter
authors.initials: JW
authors.lastname: Jukema
mesh_terms: D008078:Cholesterol, LDL / Q000097:blood*; D020022:Genetic Predisposition to Disease; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D014280:Triglycerides / Q000097:blood
chemical_list: D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014280:Triglycerides
keywords: MR–Egger; pharmacogenetics; statin therapy