Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins
Iris Postmus(Leiden University Medical Center), Stella Trompet(Leiden University Medical Center), Harshal Deshmukh(University of Dundee), Michael R. Barnes(Queen Mary University of London), Xiaohui Li(The Lundquist Institute), Helen R. Warren(Queen Mary University of London), Daniel I. Chasman(Brigham and Women's Hospital), Kaixin Zhou(University of Dundee), Benoît J. Arsenault(Montreal Heart Institute), Louise A. Donnelly(University of Dundee), Kerri L. Wiggins(University of Washington), Christy L. Avery(University of North Carolina at Chapel Hill), Paula J. Griffin(Boston University), QiPing Feng(Vanderbilt University), Kent D. Taylor(The Lundquist Institute), Guo Li(University of Washington), Daniel S. Evans(California Pacific Medical Center), Albert V. Smith(Icelandic Heart Association), Catherine E. de Keyser(Dutch Health Care Inspectorate), Andrew D. Johnson(National Heart Lung and Blood Institute), Anton J. M. de Craen(Leiden University Medical Center), David J. Stott(University of Glasgow), Brendan M. Buckley(University College Cork), Ian Ford(University of Glasgow), Rudi G. J. Westendorp(Leyden Academy on Vitality and Ageing), P. Eline Slagboom(Leiden University Medical Center), Naveed Sattar(British Heart Foundation), Patricia B. Munroe(Queen Mary University of London), Peter Sever(Imperial College London), Neil Poulter(Imperial College London), Alice Stanton(Royal College of Surgeons in Ireland), Denis C. Shields(University College Dublin), Eoin OʼBrien(University College Dublin), Sue Shaw‐Hawkins(Queen Mary University of London), Yu Chen(The Lundquist Institute), Deborah A. Nickerson(University of Washington), Joshua D. Smith(University of Washington), Marie‐Pierre Dubé(Montreal Heart Institute), S. Matthijs Boekholdt(Amsterdam UMC Location University of Amsterdam), G. Kees Hovingh(Amsterdam UMC Location University of Amsterdam), John J.P. Kastelein(Amsterdam UMC Location University of Amsterdam), Paul McKeigue(University of Edinburgh), John Betteridge(University College London), Andrew Neil(University of Oxford), Paul N. Durrington(University of Manchester), Alex S. F. Doney(University of Dundee), Fiona Carr(University of Dundee), Andrew P. Morris(University of Dundee), Mark I. McCarthy(Churchill Hospital), Leif Groop(Malmö University), Emma Ahlqvist(Malmö University), Joshua C. Bis(University of Washington), Kenneth Rice(University of Washington), Nicholas L. Smith(Group Health Cooperative), Thomas Lumley(Statistics New Zealand), Eric A. Whitsel(University of North Carolina at Chapel Hill), Til Stürmer(University of North Carolina at Chapel Hill), Eric Boerwinkle(The University of Texas Health Science Center at Houston), Julius S. Ngwa(Boston University), Christopher J. O’Donnell(Framingham Heart Study), Ramachandran S. Vasan(Boston University), Wei‐Qi Wei(Vanderbilt University), Russell A. Wilke(Sanford Health), Ching‐Ti Liu(Boston University), Fangui Sun(Boston University), Xiuqing Guo(The Lundquist Institute), Susan R. Heckbert(Group Health Cooperative), Wendy S. Post(Johns Hopkins University), Nona Sotoodehnia(University of Washington), Alice M. Arnold(University of Washington), Jeanette M. Stafford(Wake Forest University), Jingzhong Ding(Wake Forest University), David M. Herrington(Wake Forest University), Stephen B. Kritchevsky(Wake Forest University), Guðný Eiríksdóttir(Icelandic Heart Association), Leonore J. Launer(National Institutes of Health), Tamara B. Harris(National Institutes of Health), Audrey Y. Chu(Brigham and Women's Hospital), Franco Giulianini(Brigham and Women's Hospital), Jean MacFadyen(Brigham and Women's Hospital), Bryan J. Barratt(AstraZeneca (United Kingdom)), Fredrik Nyberg(AstraZeneca (Netherlands)), Bruno H. Stricker(Dutch Health Care Inspectorate), André G. Uitterlinden(Erasmus MC), Albert Hofman(Erasmus MC), Fernando Rivadeneira(Erasmus MC), Valur Emilsson(Icelandic Heart Association), Oscar H. Franco(Erasmus MC), Paul M. Ridker(Brigham and Women's Hospital), Vilmundur Guðnason(University of Iceland), Ching‐Ti Liu(Wake Forest University), Joshua C. Denny(Vanderbilt University), Christie M. Ballantyne(Baylor College of Medicine), Jerome I. Rotter(The Lundquist Institute), L. Adrienne Cupples(Framingham Heart Study), Bruce M. Psaty(Group Health Cooperative), Colin N. A. Palmer(University of Dundee), Jean‐Claude Tardif(Montreal Heart Institute), Helen M. Colhoun(University of Dundee), G. A. Hitman(Queen Mary University of London), Ronald M. Krauss, J. Wouter Jukema(Netherlands Heart Institute), Mark J. Caulfield(Queen Mary University of London), Peter Donnelly(Centre for Human Genetics), Inês Barroso(Wellcome Sanger Institute), Jenefer M. Blackwell(The Kids Research Institute Australia), Elvira Bramon(King's College London), Matthew A. Brown(The University of Queensland), Juan P. Casas(London School of Hygiene & Tropical Medicine), Aiden Corvin(Trinity College Dublin), Panos Deloukas(Wellcome Sanger Institute), Audrey Duncanson(Wellcome Trust), Janusz Jankowski(Queen Mary University of London), Hugh S. Markus(St George's, University of London), Christopher G. Mathew(Guy's Hospital), Colin N. A. Palmer(University of Dundee), Robert Plomin(King's College London), Anna Rautanen(Centre for Human Genetics), Stephen Sawcer(University of Cambridge), Richard C. Trembath(Guy's Hospital), Ananth C. Viswanathan(Moorfields Eye Hospital NHS Foundation Trust), Nicholas Wood(National Hospital for Neurology and Neurosurgery), Data and Analysis Group(Centre for Human Genetics), Chris C. A. Spencer(Centre for Human Genetics), Gavin Band(Centre for Human Genetics), Céline Bellenguez(Centre for Human Genetics), Colin L. Freeman(Centre for Human Genetics), Garrett Hellenthal(Centre for Human Genetics), Eleni Giannoulatou(Centre for Human Genetics), Matti Pirinen(Centre for Human Genetics), Richard D. Pearson(Centre for Human Genetics), Amy Strange(Centre for Human Genetics), Zhan Su(Centre for Human Genetics), Damjan Vukcevic(Centre for Human Genetics), Peter Donnelly(Wellcome Sanger Institute), DNA, Genotyping, Data QC and Informatics Group(Wellcome Sanger Institute), Cordelia Langford(Wellcome Sanger Institute), Sarah Hunt(Wellcome Sanger Institute), Sarah Edkins(Wellcome Sanger Institute), Rhian Gwilliam(Wellcome Sanger Institute), Hannah Blackburn(Wellcome Sanger Institute), Suzannah J. Bumpstead(Wellcome Sanger Institute), Serge Dronov(Wellcome Sanger Institute), Matthew Gillman(Wellcome Sanger Institute), Emma Gray(Wellcome Sanger Institute), Naomi Hammond(Wellcome Sanger Institute), Alagurevathi Jayakumar(Wellcome Sanger Institute), Owen T McCann(Wellcome Sanger Institute), Jennifer Liddle(Wellcome Sanger Institute), Simon Potter(Wellcome Sanger Institute), Rathi Ravindrarajah(Wellcome Sanger Institute), Michelle Ricketts(Wellcome Sanger Institute), Matthew Waller(Wellcome Sanger Institute), Paul A. Weston(Wellcome Sanger Institute), Sara Widaa(Wellcome Sanger Institute), Pamela Whittaker(Wellcome Sanger Institute), Ines Barroso(Guy's Hospital), Panos Deloukas(The Kids Research Institute Australia), Christopher G. Mathew(The University of Queensland), Jenefer M. Blackwell(Trinity College Dublin), Matthew A. Brown(Churchill Hospital), Aiden Corvin(Centre for Human Genetics), Mark I. McCarthy(Churchill Hospital), Chris C. A. Spencer
Cited by 279Open Access
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.
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