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

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; Christy L Avery; Paula Griffin; QiPing Feng; Kent D Taylor; Guo Li; Daniel S Evans; Albert V Smith; Catherine E de Keyser; Andrew D Johnson; Anton J M de Craen; David J Stott; Brendan M Buckley; Ian Ford; Rudi G J Westendorp; P Eline Slagboom; Naveed Sattar; Patricia B Munroe; Peter Sever; Neil Poulter; Alice Stanton; Denis C Shields; Eoin O'Brien; Sue Shaw-Hawkins; Y-D Ida Chen; Deborah A Nickerson; Joshua D Smith; Marie Pierre Dubé; S Matthijs Boekholdt; G Kees Hovingh; John J P Kastelein; Paul M McKeigue; John Betteridge; Andrew Neil; Paul N Durrington; Alex Doney; Fiona Carr; Andrew Morris; Mark I McCarthy; Leif Groop; Emma Ahlqvist; Joshua C Bis; Kenneth Rice; Nicholas L Smith; Thomas Lumley; Eric A Whitsel; Til Stürmer; Eric Boerwinkle; Julius S Ngwa; Christopher J O'Donnell; Ramachandran S Vasan; Wei-Qi Wei; Russell A Wilke; Ching-Ti Liu; Fangui Sun; Xiuqing Guo; Susan R Heckbert; Wendy Post; Nona Sotoodehnia; Alice M Arnold; Jeanette M Stafford; Jingzhong Ding; David M Herrington; Stephen B Kritchevsky; Gudny Eiriksdottir; Leonore J Launer; Tamara B Harris; Audrey Y Chu; Franco Giulianini; Jean G MacFadyen; Bryan J Barratt; Fredrik Nyberg; Bruno H Stricker; André G Uitterlinden; Albert Hofman; Fernando Rivadeneira; Valur Emilsson; Oscar H Franco; Paul M Ridker; Vilmundur Gudnason; Yongmei Liu; Joshua C Denny; Christie M Ballantyne; Jerome I Rotter; L Adrienne Cupples; Bruce M Psaty; Colin N A Palmer; Jean-Claude Tardif; Helen M Colhoun; Graham Hitman; Ronald M Krauss; J Wouter Jukema; Mark J Caulfield; Welcome Trust Case Control Consortium; Panos Deloukas

doi:10.1038/ncomms6068

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

Journal article

Open access

Peer reviewed

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

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, …

Nature communications, Vol.5(1), pp.5068-5068

28/10/2014

DOI: https://doi.org/10.1038/ncomms6068

PMCID: PMC4220464

PMID: 25350695

Abstract

Cholesterol, LDL - genetics

Genome-Wide Association Study

Humans

Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology

Pharmacogenetics

Polymorphism, Single Nucleotide - genetics

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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Title: Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins
Creators - without role: Iris Postmus - Netherlands Consortium for Healthy Ageing
Stella Trompet - Leiden University Medical Center
Harshal A Deshmukh - Ninewells Hospital
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
Benoit J Arsenault - Montreal Heart Institute
Louise A Donnelly - University of Dundee
Kerri L Wiggins - University of Washington
Christy L Avery - Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina 27599, USA
Paula 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 Research Institute, San Francisco, California 94107, USA
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 - Icelandic Heart Association
Brendan M Buckley - University College Cork
Ian Ford - University of Glasgow
Rudi G J Westendorp - Leiden University Medical Center
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 O'Brien - University College Dublin
Sue Shaw-Hawkins - Queen Mary University of London
Y-D Ida Chen - The Lundquist Institute
Deborah A Nickerson - University of Washington
Joshua D Smith - University of Washington
Marie Pierre Dubé - Université de Montréal
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 - University of Manchester
Alex Doney - University of Dundee
Fiona Carr - University of Dundee
Andrew Morris - Ninewells Hospital
Mark I McCarthy - University of Oxford
Leif Groop - Lund University
Emma Ahlqvist - Lund University
Joshua C Bis - University of Washington
Kenneth Rice - University of Washington
Nicholas L Smith - University of Washington
Thomas Lumley - University of Auckland
Eric A Whitsel - 1] Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina 27599, USA Department of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599, USA
Til Stürmer - Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina 27599, USA
Eric Boerwinkle - The University of Texas Health Science Center at Houston
Julius S Ngwa - Boston University
Christopher J O'Donnell - National Heart Lung and Blood Institute
Ramachandran S Vasan - Boston University School of Medicine
Wei-Qi Wei - Vanderbilt University
Russell A Wilke - Department of Internal Medicine, Center for IMAGENETICS, Sanford Healthcare, Fargo, North Dakota, 58104 USA
Ching-Ti Liu - Boston University
Fangui Sun - Boston University
Xiuqing Guo - The Lundquist Institute
Susan R Heckbert - University of Washington
Wendy Post - Johns Hopkins University
Nona Sotoodehnia - University of Washington
Alice M Arnold - University of Washington
Jeanette M Stafford - Division of Public Health Sciences, Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157, USA
Jingzhong Ding - Division of Public Health Sciences, Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157, USA
David M Herrington - Department of Internal Medicine, Section on Cardiology, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157, USA
Stephen B Kritchevsky - Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157, USA
Gudny Eiriksdottir - Icelandic Heart Association
Leonore J Launer - National Institute on Aging
Tamara B Harris - National Institute on Aging
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 - AstraZeneca
Fredrik Nyberg - University of Gothenburg
Bruno H Stricker - 1] Department of Epidemiology, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands Health Care Inspectorate, 2595 AN The Hague, The Netherlands Department of Internal Medicine, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands
André G Uitterlinden - Netherlands Consortium for Healthy Ageing
Albert Hofman - Netherlands Consortium for Healthy Ageing
Fernando Rivadeneira - Department of Internal Medicine, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands
Valur Emilsson - Icelandic Heart Association
Oscar H Franco - Department of Epidemiology, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands
Paul M Ridker - Brigham and Women's Hospital
Vilmundur Gudnason - University of Iceland
Yongmei Liu - Division of Public Health Sciences, Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157, USA
Joshua C Denny - Vanderbilt University
Christie M Ballantyne - Baylor College of Medicine
Jerome I Rotter - The Lundquist Institute
L Adrienne Cupples - Boston University
Bruce M Psaty - University of Washington
Colin N A Palmer - University of Dundee
Jean-Claude Tardif - Université de Montréal
Helen M Colhoun - University of Dundee
Graham Hitman - Queen Mary University of London
Ronald M Krauss - Children's Hospital Oakland Research Institute, Oakland, California 94609, USA
J Wouter Jukema - Leiden University Medical Center
Mark J Caulfield - Queen Mary University of London
Welcome Trust Case Control Consortium
Panos Deloukas - King Abdulaziz University
Publication Details: Nature communications, Vol.5(1), pp.5068-5068
Grant note: N01HC95169 / NHLBI NIH HHS Department of Health HL085251 / NHLBI NIH HHS U01 HG004402 / NHGRI NIH HHS R01 HL068986 / NHLBI NIH HHS R01 HL085251 / NHLBI NIH HHS N02-HL-6-4278 / NHLBI NIH HHS HHSN268200782096C / NHGRI NIH HHS Intramural NIH HHS R56 AG023629 / NIA NIH HHS R01 HL103612 / NHLBI NIH HHS HL087652 / NHLBI NIH HHS P30 DK079637 / NIDDK NIH HHS N01 AG062106 / NIA NIH HHS R01 HL080295 / NHLBI NIH HHS R01HL59367 / NHLBI NIH HHS HHSN268201100010C / NHLBI NIH HHS HHSN268201100005C / NHLBI NIH HHS G0400126 / Medical Research Council R01 HL059367 / NHLBI NIH HHS N01 HC-95168 / NHLBI NIH HHS N01 HC-95165 / NHLBI NIH HHS 085475/Z/08/Z / Wellcome Trust HL068986 / NHLBI NIH HHS HHSN268201100005I / NHLBI NIH HHS UL1 RR033176 / NCRR NIH HHS G952010 / Medical Research Council N01 HC095159 / NHLBI NIH HHS U19 HL065962 / NHLBI NIH HHS P30 DK063491 / NIDDK NIH HHS R01 HL087652 / NHLBI NIH HHS U01 HL080295 / NHLBI NIH HHS N01HC85083 / NHLBI NIH HHS HHSN268201100012C / NHLBI NIH HHS RR-024156 / NCRR NIH HHS R01 AG023629 / NIA NIH HHS N01-HC-25195 / NHLBI NIH HHS R01HL086694 / NHLBI NIH HHS R01 AG032098 / NIA NIH HHS R01 HL073410 / NHLBI NIH HHS U01HG004402 / NHGRI NIH HHS 085475/B/08/Z / Wellcome Trust HHSN268201200036C / NHLBI NIH HHS N01HC85082 / NHLBI NIH HHS UL1TR000124 / NCATS NIH HHS U01-HG04603 / NHGRI NIH HHS R01 HL086694 / NHLBI NIH HHS N01 HC-95166 / NHLBI NIH HHS 2 UL1 TR000445 / NCATS NIH HHS UL1 RR024156 / NCRR NIH HHS HL073410 / NHLBI NIH HHS 1R01AG032098-01A1 / NIA NIH HHS N01HC85079 / NHLBI NIH HHS N01 HC-95160 / NHLBI NIH HHS HHSN268200625226C / PHS HHS N01 AG062103 / NIA NIH HHS HHSN268201100007C / NHLBI NIH HHS N01-AG-1-2100 / NIA NIH HHS N01 HC-95164 / NHLBI NIH HHS PG/13/66/30442 / British Heart Foundation N01 HC-95161 / NHLBI NIH HHS UL1 TR000445 / NCATS NIH HHS HHSN268201100005G / NHLBI NIH HHS N01 HC-95167 / NHLBI NIH HHS N01 HC-95159 / NHLBI NIH HHS HHSN268201100011C / NHLBI NIH HHS HHSN268201100011I / NHLBI NIH HHS HHSN268201100007I / NHLBI NIH HHS R01HL103612 / NHLBI NIH HHS HL105756 / NHLBI NIH HHS UL1 RR025005 / NCRR NIH HHS U19 HL069757 / NHLBI NIH HHS MR/K006584/1 / Medical Research Council N01HC25195 / NHLBI NIH HHS N01HC85081 / NHLBI NIH HHS N01HC85086 / NHLBI NIH HHS UL1 RR024975 / NCRR NIH HHS N01 HC-95169 / NHLBI NIH HHS RC2-GM092318 / NIGMS NIH HHS HHSN268201100008I / NHLBI NIH HHS R01HL087641 / NHLBI NIH HHS N01HC85080 / NHLBI NIH HHS N01 HC-95162 / NHLBI NIH HHS HHSN268201100006C / NHLBI NIH HHS U01 HG004603 / NHGRI NIH HHS UL1 TR000124 / NCATS NIH HHS 084727/Z/08/Z / Wellcome Trust G9521010 / Medical Research Council HHSN268200800007C / NHLBI NIH HHS N01HC55222 / NHLBI NIH HHS N01 AG062101 / NIA NIH HHS HL103612 / NHLBI NIH HHS UL1RR025005 / NCRR NIH HHS HHSN268201100008C / NHLBI NIH HHS R01 HL105756 / NHLBI NIH HHS R01 HL087641 / NHLBI NIH HHS HHSN268201100009C / NHLBI NIH HHS UL1RR033176 / NCRR NIH HHS HL080295 / NHLBI NIH HHS N01 HC-95163 / NHLBI NIH HHS DK063491 / NIDDK NIH HHS HHSN268201100009I / NHLBI NIH HHS AG023629 / NIA NIH HHS
Identifiers: 9936662908331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article