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

Welcome Trust Case Control Consortium

doi:10.1038/ncomms6068

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

Welcome Trust Case Control Consortium

Research output: Contribution to journal › Article › peer-review

Original language	English (US)
Article number	5068
Journal	Nature communications
Volume	5
DOIs	https://doi.org/10.1038/ncomms6068
State	Published - 2014
Externally published	Yes

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General
General Physics and Astronomy

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10.1038/ncomms6068

Cite this

@article{90ae016de46e4daeaa9616c1caa9d943,

title = "Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins",

author = "\{Welcome Trust Case Control Consortium\} and Iris Postmus and Stella Trompet and Deshmukh, \{Harshal A.\} and Barnes, \{Michael R.\} and Xiaohui Li and Warren, \{Helen R.\} and Chasman, \{Daniel I.\} and Kaixin Zhou and Arsenault, \{Benoit J.\} and Donnelly, \{Louise A.\} and Wiggins, \{Kerri L.\} and Avery, \{Christy L.\} and Paula Griffin and Qiping Feng and Taylor, \{Kent D.\} and Guo Li and Evans, \{Daniel S.\} and Smith, \{Albert V.\} and \{De Keyser\}, \{Catherine E.\} and Johnson, \{Andrew D.\} and \{De Craen\}, \{Anton J.M.\} and Stott, \{David J.\} and Buckley, \{Brendan M.\} and Ian Ford and Westendorp, \{Rudi G.J.\} and Slagboom, \{P. Eline\} and Naveed Sattar and Munroe, \{Patricia B.\} and Peter Sever and Neil Poulter and Alice Stanton and Shields, \{Denis C.\} and Eoin O'Brien and Sue Shaw-Hawkins and \{Ida Chen\}, \{Y. D.\} and Nickerson, \{Deborah A.\} and Smith, \{Joshua D.\} and Dub{\'e}, \{Marie Pierre\} and Boekholdt, \{S. Matthijs\} and Hovingh, \{G. Kees\} and Kastelein, \{John J.P.\} and McKeigue, \{Paul M.\} and John Betteridge and Andrew Neil and Durrington, \{Paul N.\} and Alex Doney and Fiona Carr and Andrew Morris and McCarthy, \{Mark I.\} and Vasan, \{Ramachandran S.\}",

note = "Funding Information: ASCOT: The Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) trial was funded by an investigator-initiated grant from Pfizer, USA. The study was investigator led and was conducted, analysed and reported independently of the company. The Genomewide Association Scan was funded by the National Institutes for Health Research (NIHR) as part of the portfolio of translational research of the NIHR Biomedical Research Unit at Barts and the NIHR Biomedical Research Centre at Imperial College, the International Centre for Circulatory Health Charity and the Medical Research Council through G952010. On behalf of the ASCOT investigators, we thank all ASCOT trial participants, physicians, nurses, and practices in the participating countries for their important contribution to the study. Funding Information: Rotterdam study: The Rotterdam Study is supported by the Erasmus Medical Center and Erasmus University Rotterdam; the Netherlands Organization for Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly; the Ministry of Education, Culture and Science; the Ministry of Health Welfare and Sports; and the European Commission and Municipality of Rotterdam. This work was supported by the Netherlands Genomics Initiative (NGI) Netherlands Organization for Scietific Research (NOW; 050-060-810). Funding Information: MESA: The Multi-Ethnic Study of Atherosclerosis (MESA) and MESA SNP Health Association Resource (SHARe) are conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with MESA investigators. Support is provided by grants and contracts N01 HC-95159 through N01-HC-95169 and RR-024156. Additional funding was supported in part by the Clinical Translational Science Institute grant UL1RR033176 and is now at the National Center for Advancing Translational Sciences, CTSI grant UL1TR000124. We thank the other investigators in the Pharmarcogenetics Working Group, the staff and the participants of the MESA study for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org. JUPITER: Genetic analysis in JUPITER was supported by a research grant from AstraZeneca to D.C. and P.M. Funding Information: HVH: This Heart and Vascular Health Study research was supported by NHLBI grants HL085251, HL073410, HL085251 and HL068986. Funding Information: Health ABC: The Health ABC study was supported by NIA contracts N01AG62101, N01AG62103 and N01AG62106. The genome-wide association study was funded by NIA grant 1R01AG032098-01A1 to Wake Forest University Health Sciences and genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University, contract number HHSN268200782096C. This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging. Funding Information: GoDARTS: We are grateful to all the participants who took part in this study, to the general practitioners, to the Scottish School of Primary Care for their help in recruiting the participants and to the whole team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists and nurses. The Wellcome Trust provides support for Wellcome Trust United Kingdom Type 2 Diabetes Case Control Collection (GoDARTS) and informatics support is provided by the Chief Scientist Office. The Wellcome Trust funds the Scottish Health Informatics Programme, provides core support for the Wellcome Trust Centre for Human Genetics in Oxford and funds the Wellcome Trust Case Control Consortium. This research was specifically funded by Diabetes UK (07/0003525) and the Wellcome Trust (084727/Z/08/Z, 085475/Z/08/Z and 085475/B/08/Z). Genotyping of the GoD-ARTS samples (sample 2) was also funded as part of the EU IMI-SUMMIT programme. K.Z. holds a Henry Wellcome Post-Doctoral Fellowship. Funding Information: Data from the Heart Protection Study have been contributed by Heart Protection Study Collaborative Group6. PROSPER/PHASE: The Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) trial was supported by an investigator-initiated grant from Bristol-Myers Squibb, USA. The study was conducted, analysed and reported independently of the company. The GWAS project PHASE has received funding from the European Union{\textquoteright}s Seventh Framework Programme (FP7/2007–2013) under grant agreement HEALTH-F2-2009-223004. A part of the genotyping was funded by The Netherlands Consortium for Healthy Ageing (NGI: 05060810). Professor Dr J.W.J. is an established clinical investigator of The Netherlands Heart Foundation (2001 D 032). Funding Information: Framingham HS: The Framingham Heart Study work was supported by the National Heart Lung and Blood Institute of the National Institutes of Health and Boston University School of Medicine (Contract No. N01-HC-25195), its contract with Affymetrix, Inc. for genotyping services (Contract No. N02-HL-6-4278) and based on analyses by Framingham Heart Study investigators participating in the SNP Health Association Resource (SHARe) project. A portion of this research was conducted using the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center, also supported by R01HL103612 (PI psaty, subcontract PI, Vasan). Funding Information: PARC: This research was supported by the National Institutes of Health: grant U19 HL069757 from the National Heart, Lung, and Blood Institute, and grant UL1TR000124 from the National Center for Advancing Translational Sciences. Funding Information: CHS: This CHS research was supported by NHLBI contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083 and N01HC85086; and NHLBI grants HL080295, HL087652, HL105756 and HL103612 with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided through AG023629 from the National Institute on Aging (NIA). A full list of CHS investigators and institutions can be found at http://www.chs-nhlbi.org/pi.htm. The provision of genotyping data was supported in part by the National Center for Advancing Translational Sciences, CTSI grant UL1TR000124, and the National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) grant DK063491 to the Southern California Diabetes Endocrinology Research Center. Funding Information: CARDS: We thank the other investigators, the staff and the participants of the CARDS study. A full list of CARDS investigators can be found in original CARDS paper71. CARDS was funded by grants to the Universities of London and Manchester by Pfizer, Diabetes UK and the Department of Health. Funding Information: BioVU: BioVU receives support through the National Center for Research Resources UL1 RR024975, which is now the National Center for Advancing Translational Sciences, 2 UL1 TR000445. Genotyping was supported via grant U01-HG04603 from the National Human Genome Research Institute and RC2-GM092318 from the National Insitute of General Medical Sciences. Funding Information: Supplementary Information accompanies this paper at http://www.nature.com/ naturecommunications Competing financial interests: B.M.P. serves on the Data and Safety Monitoring Board of a clinical trial funded by the device manufacturer (Zoll LifeCor). N.P. and A.S. received funding from Pfizer for the extended follow-up of the ASCOT UK participants. D.I.C. and P.M.R. received research support for independent genetic analysis in JUPITER from AstraZeneca. F.N. and B.J.B. have employment, stock and stock options in AstraZeneca, a for-profit company engaged in the discovery, development, manufacture and marketing of proprietary therapeutics such as rosuvastatin, but do not consider that this creates any conflict of interest with the subject–matter of this publication. R.M.K. serves on the Merck Global Atherosclerosis Advisory Board. The remaining authors declare no competing financial interests. Funding Information: AGES: This study has been funded by NIH contract N01-AG-1-2100, the NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association) and the Althingi (the Icelandic Parliament). The study is approved by the Icelandic National Bioethics Committee, VSN: 00-063. The researchers are indebted to the participants for their willingness to participate in the study. Funding Information: ARIC: The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C and HHSN268201100012C), R01HL087641, R01HL59367 and R01HL086694; National Human Genome Research Institute contract U01HG004402; and National Institutes of Health contract HHSN268200625226C. We thank the staff and participants of the ARIC study for their important contributions. Infrastructure was partly supported by Grant Number UL1RR025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research.",

year = "2014",

doi = "10.1038/ncomms6068",

language = "English (US)",

volume = "5",

journal = "Nature communications",

issn = "2041-1723",

publisher = "Nature Research",

}

TY - JOUR

T1 - Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins

AU - Welcome Trust Case Control Consortium

AU - Postmus, Iris

AU - Trompet, Stella

AU - Deshmukh, Harshal A.

AU - Barnes, Michael R.

AU - Li, Xiaohui

AU - Warren, Helen R.

AU - Chasman, Daniel I.

AU - Zhou, Kaixin

AU - Arsenault, Benoit J.

AU - Donnelly, Louise A.

AU - Wiggins, Kerri L.

AU - Avery, Christy L.

AU - Griffin, Paula

AU - Feng, Qiping

AU - Taylor, Kent D.

AU - Li, Guo

AU - Evans, Daniel S.

AU - Smith, Albert V.

AU - De Keyser, Catherine E.

AU - Johnson, Andrew D.

AU - De Craen, Anton J.M.

AU - Stott, David J.

AU - Buckley, Brendan M.

AU - Ford, Ian

AU - Westendorp, Rudi G.J.

AU - Slagboom, P. Eline

AU - Sattar, Naveed

AU - Munroe, Patricia B.

AU - Sever, Peter

AU - Poulter, Neil

AU - Stanton, Alice

AU - Shields, Denis C.

AU - O'Brien, Eoin

AU - Shaw-Hawkins, Sue

AU - Ida Chen, Y. D.

AU - Nickerson, Deborah A.

AU - Smith, Joshua D.

AU - Dubé, Marie Pierre

AU - Boekholdt, S. Matthijs

AU - Hovingh, G. Kees

AU - Kastelein, John J.P.

AU - McKeigue, Paul M.

AU - Betteridge, John

AU - Neil, Andrew

AU - Durrington, Paul N.

AU - Doney, Alex

AU - Carr, Fiona

AU - Morris, Andrew

AU - McCarthy, Mark I.

AU - Vasan, Ramachandran S.

N1 - Funding Information: ASCOT: The Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) trial was funded by an investigator-initiated grant from Pfizer, USA. The study was investigator led and was conducted, analysed and reported independently of the company. The Genomewide Association Scan was funded by the National Institutes for Health Research (NIHR) as part of the portfolio of translational research of the NIHR Biomedical Research Unit at Barts and the NIHR Biomedical Research Centre at Imperial College, the International Centre for Circulatory Health Charity and the Medical Research Council through G952010. On behalf of the ASCOT investigators, we thank all ASCOT trial participants, physicians, nurses, and practices in the participating countries for their important contribution to the study. Funding Information: Rotterdam study: The Rotterdam Study is supported by the Erasmus Medical Center and Erasmus University Rotterdam; the Netherlands Organization for Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly; the Ministry of Education, Culture and Science; the Ministry of Health Welfare and Sports; and the European Commission and Municipality of Rotterdam. This work was supported by the Netherlands Genomics Initiative (NGI) Netherlands Organization for Scietific Research (NOW; 050-060-810). Funding Information: MESA: The Multi-Ethnic Study of Atherosclerosis (MESA) and MESA SNP Health Association Resource (SHARe) are conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with MESA investigators. Support is provided by grants and contracts N01 HC-95159 through N01-HC-95169 and RR-024156. Additional funding was supported in part by the Clinical Translational Science Institute grant UL1RR033176 and is now at the National Center for Advancing Translational Sciences, CTSI grant UL1TR000124. We thank the other investigators in the Pharmarcogenetics Working Group, the staff and the participants of the MESA study for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org. JUPITER: Genetic analysis in JUPITER was supported by a research grant from AstraZeneca to D.C. and P.M. Funding Information: HVH: This Heart and Vascular Health Study research was supported by NHLBI grants HL085251, HL073410, HL085251 and HL068986. Funding Information: Health ABC: The Health ABC study was supported by NIA contracts N01AG62101, N01AG62103 and N01AG62106. The genome-wide association study was funded by NIA grant 1R01AG032098-01A1 to Wake Forest University Health Sciences and genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University, contract number HHSN268200782096C. This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging. Funding Information: GoDARTS: We are grateful to all the participants who took part in this study, to the general practitioners, to the Scottish School of Primary Care for their help in recruiting the participants and to the whole team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists and nurses. The Wellcome Trust provides support for Wellcome Trust United Kingdom Type 2 Diabetes Case Control Collection (GoDARTS) and informatics support is provided by the Chief Scientist Office. The Wellcome Trust funds the Scottish Health Informatics Programme, provides core support for the Wellcome Trust Centre for Human Genetics in Oxford and funds the Wellcome Trust Case Control Consortium. This research was specifically funded by Diabetes UK (07/0003525) and the Wellcome Trust (084727/Z/08/Z, 085475/Z/08/Z and 085475/B/08/Z). Genotyping of the GoD-ARTS samples (sample 2) was also funded as part of the EU IMI-SUMMIT programme. K.Z. holds a Henry Wellcome Post-Doctoral Fellowship. Funding Information: Data from the Heart Protection Study have been contributed by Heart Protection Study Collaborative Group6. PROSPER/PHASE: The Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) trial was supported by an investigator-initiated grant from Bristol-Myers Squibb, USA. The study was conducted, analysed and reported independently of the company. The GWAS project PHASE has received funding from the European Union’s Seventh Framework Programme (FP7/2007–2013) under grant agreement HEALTH-F2-2009-223004. A part of the genotyping was funded by The Netherlands Consortium for Healthy Ageing (NGI: 05060810). Professor Dr J.W.J. is an established clinical investigator of The Netherlands Heart Foundation (2001 D 032). Funding Information: Framingham HS: The Framingham Heart Study work was supported by the National Heart Lung and Blood Institute of the National Institutes of Health and Boston University School of Medicine (Contract No. N01-HC-25195), its contract with Affymetrix, Inc. for genotyping services (Contract No. N02-HL-6-4278) and based on analyses by Framingham Heart Study investigators participating in the SNP Health Association Resource (SHARe) project. A portion of this research was conducted using the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center, also supported by R01HL103612 (PI psaty, subcontract PI, Vasan). Funding Information: PARC: This research was supported by the National Institutes of Health: grant U19 HL069757 from the National Heart, Lung, and Blood Institute, and grant UL1TR000124 from the National Center for Advancing Translational Sciences. Funding Information: CHS: This CHS research was supported by NHLBI contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083 and N01HC85086; and NHLBI grants HL080295, HL087652, HL105756 and HL103612 with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided through AG023629 from the National Institute on Aging (NIA). A full list of CHS investigators and institutions can be found at http://www.chs-nhlbi.org/pi.htm. The provision of genotyping data was supported in part by the National Center for Advancing Translational Sciences, CTSI grant UL1TR000124, and the National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) grant DK063491 to the Southern California Diabetes Endocrinology Research Center. Funding Information: CARDS: We thank the other investigators, the staff and the participants of the CARDS study. A full list of CARDS investigators can be found in original CARDS paper71. CARDS was funded by grants to the Universities of London and Manchester by Pfizer, Diabetes UK and the Department of Health. Funding Information: BioVU: BioVU receives support through the National Center for Research Resources UL1 RR024975, which is now the National Center for Advancing Translational Sciences, 2 UL1 TR000445. Genotyping was supported via grant U01-HG04603 from the National Human Genome Research Institute and RC2-GM092318 from the National Insitute of General Medical Sciences. Funding Information: Supplementary Information accompanies this paper at http://www.nature.com/ naturecommunications Competing financial interests: B.M.P. serves on the Data and Safety Monitoring Board of a clinical trial funded by the device manufacturer (Zoll LifeCor). N.P. and A.S. received funding from Pfizer for the extended follow-up of the ASCOT UK participants. D.I.C. and P.M.R. received research support for independent genetic analysis in JUPITER from AstraZeneca. F.N. and B.J.B. have employment, stock and stock options in AstraZeneca, a for-profit company engaged in the discovery, development, manufacture and marketing of proprietary therapeutics such as rosuvastatin, but do not consider that this creates any conflict of interest with the subject–matter of this publication. R.M.K. serves on the Merck Global Atherosclerosis Advisory Board. The remaining authors declare no competing financial interests. Funding Information: AGES: This study has been funded by NIH contract N01-AG-1-2100, the NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association) and the Althingi (the Icelandic Parliament). The study is approved by the Icelandic National Bioethics Committee, VSN: 00-063. The researchers are indebted to the participants for their willingness to participate in the study. Funding Information: ARIC: The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C and HHSN268201100012C), R01HL087641, R01HL59367 and R01HL086694; National Human Genome Research Institute contract U01HG004402; and National Institutes of Health contract HHSN268200625226C. We thank the staff and participants of the ARIC study for their important contributions. Infrastructure was partly supported by Grant Number UL1RR025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research.

PY - 2014

Y1 - 2014

UR - https://www.scopus.com/pages/publications/84919752308

UR - https://www.scopus.com/pages/publications/84919752308#tab=citedBy

U2 - 10.1038/ncomms6068

DO - 10.1038/ncomms6068

M3 - Article

C2 - 25350695

AN - SCOPUS:84919752308

SN - 2041-1723

VL - 5

JO - Nature communications

JF - Nature communications

M1 - 5068

ER -

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

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