Biological, clinical and population relevance of 95 loci for blood lipids

Tanya M. Teslovich, Kiran Musunuru, Albert V. Smith, Andrew C. Edmondson, Ioannis M. Stylianou, Masahiro Koseki, James P. Pirruccello, Samuli Ripatti, Daniel I. Chasman, Cristen J. Willer, Christopher T. Johansen, Sigrid W. Fouchier, Aaron Isaacs, Gina M. Peloso, Maja Barbalic, Sally L. Ricketts, Joshua C. Bis, Yurii S. Aulchenko, Gudmar Thorleifsson, Mary F. Feitosa, John Chambers, Marju Orho-Melander, Olle Melander, Toby Johnson, Xiaohui Li, Xiuqing Guo, Mingyao Li, Yoon Shin Cho, Min Jin Go, Young Jin Kim, Jong-Young Lee, Taesung Park, Kyunga Kim, Xueling Sim, Rick Twee-Hee Ong, Damien C. Croteau-Chonka, Leslie A. Lange, Joshua D. Smith, Kijoung Song, Jing Hua Zhao, Xin Yuan, Jian’an Luan, Claudia Lamina, Andreas Ziegler, Weihua Zhang, Robert Y. L. Zee, Alan F. Wright, Jacqueline C. M. Witteman, James F. Wilson, Gonneke Willemsen, H.-Erich Wichmann, John B. Whitfield, Dawn M. Waterworth, Nicholas J. Wareham, Gérard Waeber, Peter Vollenweider, Benjamin F. Voight, Veronique Vitart, Andre G. Uitterlinden, Manuela Uda, Jaakko Tuomilehto, John R. Thompson, Toshiko Tanaka, Ida Surakka, Heather M. Stringham, Tim D. Spector, Nicole Soranzo, Johannes H. Smit, Juha Sinisalo, Kaisa Silander, Eric J. G. Sijbrands, Angelo Scuteri, James Scott, David Schlessinger, Serena Sanna, Veikko Salomaa, Juha Saharinen, Chiara Sabatti, Aimo Ruokonen, Igor Rudan, Lynda M. Rose, Robert Roberts, Mark Rieder, Bruce M. Psaty, Peter P. Pramstaller, Irene Pichler, Markus Perola, Brenda W. J. H. Penninx, Nancy L. Pedersen, Cristian Pattaro, Alex N. Parker, Guillaume Pare, Ben A. Oostra, Christopher J. O’Donnell, Markku S. Nieminen, Deborah A. Nickerson, Grant W. Montgomery, Thomas Meitinger, Ruth McPherson, Mark I. McCarthy, Wendy McArdle, David Masson, Nicholas G. Martin, Fabio Marroni, Massimo Mangino, Patrik K. E. Magnusson, Gavin Lucas, Robert Luben, Ruth J. F. Loos, Marja-Liisa Lokki, Guillaume Lettre, Claudia Langenberg, Lenore J. Launer, Edward G. Lakatta, Reijo Laaksonen, Kirsten O. Kyvik, Florian Kronenberg, Inke R. König, Kay-Tee Khaw, Jaakko Kaprio, Lee M. Kaplan, Åsa Johansson, Marjo-Riitta Jarvelin, A. Cecile J. W. Janssens, Erik Ingelsson, Wilmar Igl, G. Kees Hovingh, Jouke-Jan Hottenga, Albert Hofman, Andrew A. Hicks, Christian Hengstenberg, Iris M. Heid, Caroline Hayward, Aki S. Havulinna, Nicholas D. Hastie, Tamara B. Harris, Talin Haritunians, Alistair S. Hall, Ulf Gyllensten, Candace Guiducci, Leif C. Groop, Elena Gonzalez, Christian Gieger, Nelson B. Freimer, Luigi Ferrucci, Jeanette Erdmann, Paul Elliott, Kenechi G. Ejebe, Angela Döring, Anna F. Dominiczak, Serkalem Demissie, Panagiotis Deloukas, Eco J. C. de Geus, Ulf de Faire, Gabriel Crawford, Francis S. Collins, Yii- der I. Chen, Mark J. Caulfield, Harry Campbell, Noel P. Burtt, Lori L. Bonnycastle, Dorret I. Boomsma, S. Matthijs Boekholdt, Richard N. Bergman, Inês Barroso, Stefania Bandinelli, Christie M. Ballantyne, Themistocles L. Assimes, Thomas Quertermous, David Altshuler, Mark Seielstad, Tien Y. Wong, E-Shyong Tai, Alan B. Feranil, Christopher W. Kuzawa, Linda S. Adair, Herman A. Taylor, Ingrid B. Borecki, Stacey B. Gabriel, James G. Wilson, Hilma Holm, Unnur Thorsteinsdottir, Vilmundur Gudnason, Ronald M. Krauss, Karen L. Mohlke, Jose M. Ordovas, Patricia B. Munroe, Jaspal S. Kooner, Alan R. Tall, Robert A. Hegele, John J.P. Kastelein, Eric E. Schadt, Jerome I. Rotter, Eric Boerwinkle, David P. Strachan, Vincent Mooser, Kari Stefansson, Muredach P. Reilly, Nilesh J Samani, Heribert Schunkert, L. Adrienne Cupples, Manjinder S. Sandhu, Paul M Ridker, Daniel J. Rader, Cornelia M. van Duijn, Leena Peltonen, Gonçalo R. Abecasis, Michael Boehnke and Sekar Kathiresan ()
Additional contact information
Tanya M. Teslovich: Center for Statistical Genetics, University of Michigan
Kiran Musunuru: Center for Human Genetic Research, Massachusetts General Hospital
Albert V. Smith: Icelandic Heart Association, Heart Preventive Clinic and Research Institute
Andrew C. Edmondson: Cardiovascular Institute, University of Pennsylvania School of Medicine
Ioannis M. Stylianou: Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine
Masahiro Koseki: Columbia University
James P. Pirruccello: Center for Human Genetic Research, Massachusetts General Hospital
Samuli Ripatti: Institute for Molecular Medicine Finland FIMM, University of Helsinki
Daniel I. Chasman: Brigham and Women’s Hospital
Cristen J. Willer: Center for Statistical Genetics, University of Michigan
Christopher T. Johansen: Robarts Research Institute, University of Western Ontario
Sigrid W. Fouchier: Academic Medical Centre at the University of Amsterdam
Aaron Isaacs: Erasmus University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
Gina M. Peloso: Boston University School of Public Health
Maja Barbalic: Human Genetics Center, University of Texas Health Science Center at Houston
Sally L. Ricketts: Strangeways Research Laboratory, University of Cambridge
Joshua C. Bis: University of Washington
Yurii S. Aulchenko: Erasmus University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
Gudmar Thorleifsson: deCODE Genetics
Mary F. Feitosa: Washington University School of Medicine
John Chambers: Imperial College London
Marju Orho-Melander: Lund University
Olle Melander: Lund University
Toby Johnson: Clinical Pharmacology and Barts and the London Genome Centre, William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London
Xiaohui Li: Medical Genetics Institute, Cedars-Sinai Medical Center
Xiuqing Guo: Medical Genetics Institute, Cedars-Sinai Medical Center
Mingyao Li: Cardiovascular Institute, University of Pennsylvania School of Medicine
Yoon Shin Cho: Center for Genome Science, National Institute of Health
Min Jin Go: Center for Genome Science, National Institute of Health
Young Jin Kim: Center for Genome Science, National Institute of Health
Jong-Young Lee: Center for Genome Science, National Institute of Health
Taesung Park: Interdisciplinary Program in Bioinformatics, College of Natural Sciences, Seoul National University
Kyunga Kim: Sookmyung Women’s University
Xueling Sim: Centre for Molecular Epidemiology, National University of Singapore
Rick Twee-Hee Ong: Genome Institute of Singapore
Damien C. Croteau-Chonka: University of North Carolina
Leslie A. Lange: University of North Carolina
Joshua D. Smith: University of Washington
Kijoung Song: GlaxoSmithKline R&D
Jing Hua Zhao: MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke’s Hospital
Xin Yuan: GlaxoSmithKline R&D
Jian’an Luan: MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke’s Hospital
Claudia Lamina: Molecular and Clinical Pharmacology, Innsbruck Medical University, Schoepfstrasse 41, A-6020 Innsbruck, Austria.
Andreas Ziegler: Institut für Medizinische Biometrie und Statistik, Universität zu Lübeck
Weihua Zhang: Imperial College London
Robert Y. L. Zee: Brigham and Women’s Hospital
Alan F. Wright: MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine
Jacqueline C. M. Witteman: Erasmus University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
James F. Wilson: Centre for Population Health Sciences, University of Edinburgh
Gonneke Willemsen: VU University Amsterdam, Van der Boechorststraat 1, 1081 BT Amsterdam, The Netherlands.
H.-Erich Wichmann: Institute of Epidemiology, Helmholtz Zentrum Munchen – German Research Center for Environmental Health
John B. Whitfield: Genetic Epidemiology Unit, Queensland Institute of Medical Research, PO Royal Brisbane Hospital
Dawn M. Waterworth: GlaxoSmithKline R&D
Nicholas J. Wareham: MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke’s Hospital
Gérard Waeber: Centre Hospitalier Universitaire Vaudois
Peter Vollenweider: Centre Hospitalier Universitaire Vaudois
Benjamin F. Voight: Center for Human Genetic Research, Massachusetts General Hospital
Veronique Vitart: MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine
Andre G. Uitterlinden: Erasmus University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
Manuela Uda: Istituto di Neurogenetica e Neurofarmacologia (INN), Consiglio Nazionale delle Ricerche, c/o Cittadella Universitaria di Monserrato, Monserrato, Cagliari 09042, Italy.
Jaakko Tuomilehto: National Institute for Health and Welfare
John R. Thompson: University of Leicester
Toshiko Tanaka: Clinical Research Branch, National Institute on Aging, National Institutes of Health
Ida Surakka: Institute for Molecular Medicine Finland FIMM, University of Helsinki
Heather M. Stringham: Center for Statistical Genetics, University of Michigan
Tim D. Spector: King’s College London
Nicole Soranzo: King’s College London
Johannes H. Smit: EMGO Institute, Neuroscience Campus Amsterdam, VU University Medical Center
Juha Sinisalo: Helsinki University Central Hospital (HUCH)
Kaisa Silander: Institute for Molecular Medicine Finland FIMM, University of Helsinki
Eric J. G. Sijbrands: Erasmus University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
Angelo Scuteri: Unita Operativa Geriatria, Istituto Nazionale Ricovero e Cura Anziani (INRCA), Istituto Ricovero e Cura a Carattere Scientifico (IRCCS), Via Cassia 1167, 00189 Rome, Italy.
James Scott: Hammersmith Hospital, National Heart and Lung Institute, Imperial College London
David Schlessinger: Gerontology Research Center, National Institute on Aging, 5600 Nathan Shock Drive, Baltimore, Maryland 21224, USA.
Serena Sanna: Istituto di Neurogenetica e Neurofarmacologia (INN), Consiglio Nazionale delle Ricerche, c/o Cittadella Universitaria di Monserrato, Monserrato, Cagliari 09042, Italy.
Veikko Salomaa: National Institute for Health and Welfare
Juha Saharinen: Institute for Molecular Medicine Finland FIMM, University of Helsinki
Chiara Sabatti: Stanford University
Aimo Ruokonen: University of Oulu
Igor Rudan: Centre for Population Health Sciences, University of Edinburgh
Lynda M. Rose: Brigham and Women’s Hospital
Robert Roberts: The John & Jennifer Ruddy Canadian Cardiovascular Genetics Centre, University of Ottawa
Mark Rieder: University of Washington
Bruce M. Psaty: Epidemiology, and Health Services, University of Washington, Group Health Research Institute, Group Health Cooperative
Peter P. Pramstaller: Institute of Genetic Medicine, European Academy Bozen/Bolzano (EURAC), Viale Druso 1, 39100 Bolzano, Italy – affiliated institute of the University of Lübeck
Irene Pichler: Institute of Genetic Medicine, European Academy Bozen/Bolzano (EURAC), Viale Druso 1, 39100 Bolzano, Italy – affiliated institute of the University of Lübeck
Markus Perola: Institute for Molecular Medicine Finland FIMM, University of Helsinki
Brenda W. J. H. Penninx: EMGO Institute, Neuroscience Campus Amsterdam, VU University Medical Center
Nancy L. Pedersen: Karolinska Institutet
Cristian Pattaro: Institute of Genetic Medicine, European Academy Bozen/Bolzano (EURAC), Viale Druso 1, 39100 Bolzano, Italy – affiliated institute of the University of Lübeck
Alex N. Parker: Amgen, Thousand Oaks, California 91320, USA.
Guillaume Pare: Genetic and Molecular Epidemiology Laboratory, McMaster University
Ben A. Oostra: Erasmus University Medical Center
Christopher J. O’Donnell: National Heart, Lung and Blood Institute’s Framingham Heart Study
Markku S. Nieminen: Helsinki University Central Hospital (HUCH)
Deborah A. Nickerson: University of Washington
Grant W. Montgomery: Genetic Epidemiology Unit, Queensland Institute of Medical Research, PO Royal Brisbane Hospital
Thomas Meitinger: Institut fur Humangenetik, Helmholtz Zentrum Munchen, Deutsches Forschungszentrum fur Umwelt und Gesundheit
Ruth McPherson: The John & Jennifer Ruddy Canadian Cardiovascular Genetics Centre, University of Ottawa
Mark I. McCarthy: Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
Wendy McArdle: Avon Longitudinal Study of Parents and Children, University of Bristol
David Masson: Columbia University
Nicholas G. Martin: Genetic Epidemiology Unit, Queensland Institute of Medical Research, PO Royal Brisbane Hospital
Fabio Marroni: Institute of Applied Genomics, via Linussio 51, 33100 Udine, Italy.
Massimo Mangino: King’s College London
Patrik K. E. Magnusson: Karolinska Institutet
Gavin Lucas: Cardiovascular Epidemiology and Genetics, Institut Municipal d’Investigacio Medica
Robert Luben: Strangeways Research Laboratory, University of Cambridge
Ruth J. F. Loos: MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke’s Hospital
Marja-Liisa Lokki: Transplantation Laboratory, Haartman Institute, University of Helsinki
Guillaume Lettre: Montreal Heart Institute (Research Center), Université de Montréal
Claudia Langenberg: MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke’s Hospital
Lenore J. Launer: Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, National Institutes of Health
Edward G. Lakatta: Gerontology Research Center, National Institute on Aging, 5600 Nathan Shock Drive, Baltimore, Maryland 21224, USA.
Reijo Laaksonen: Science Center, Tampere University Hospital
Kirsten O. Kyvik: Institute of Regional Health Research and the Danish Twin Registry, Institute of Public Health, University of Southern Denmark, JBWinsløws Vej 9B, DK-5000, Odense, Denmark.
Florian Kronenberg: Molecular and Clinical Pharmacology, Innsbruck Medical University, Schoepfstrasse 41, A-6020 Innsbruck, Austria.
Inke R. König: Institut für Medizinische Biometrie und Statistik, Universität zu Lübeck
Kay-Tee Khaw: Strangeways Research Laboratory, University of Cambridge
Jaakko Kaprio: Institute for Molecular Medicine Finland FIMM, University of Helsinki
Lee M. Kaplan: Massachusetts General Hospital Weight Center
Åsa Johansson: Rudbeck Laboratory, University of Uppsala
Marjo-Riitta Jarvelin: Imperial College London, St Mary’s Campus, Norfolk Place, London W2 1PG, UK.
A. Cecile J. W. Janssens: Erasmus University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
Erik Ingelsson: Karolinska Institutet
Wilmar Igl: Rudbeck Laboratory, University of Uppsala
G. Kees Hovingh: Academic Medical Centre at the University of Amsterdam
Jouke-Jan Hottenga: VU University Amsterdam, Van der Boechorststraat 1, 1081 BT Amsterdam, The Netherlands.
Albert Hofman: Erasmus University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
Andrew A. Hicks: Institute of Genetic Medicine, European Academy Bozen/Bolzano (EURAC), Viale Druso 1, 39100 Bolzano, Italy – affiliated institute of the University of Lübeck
Christian Hengstenberg: Klinik und Poliklinik für Innere Medizin II, Universität Regensburg
Iris M. Heid: Institute of Epidemiology, Helmholtz Zentrum Munchen – German Research Center for Environmental Health
Caroline Hayward: MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine
Aki S. Havulinna: National Institute for Health and Welfare
Nicholas D. Hastie: MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine
Tamara B. Harris: Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, National Institutes of Health
Talin Haritunians: Medical Genetics Institute, Cedars-Sinai Medical Center
Alistair S. Hall: LIGHT Research Institute, Faculty of Medicine and Health, University of Leeds
Ulf Gyllensten: Rudbeck Laboratory, University of Uppsala
Candace Guiducci: Broad Institute
Leif C. Groop: Lund University
Elena Gonzalez: Broad Institute
Christian Gieger: Institute of Epidemiology, Helmholtz Zentrum Munchen – German Research Center for Environmental Health
Nelson B. Freimer: Center for Neurobehavioral Genetics, The Jane and Terry Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California
Luigi Ferrucci: Clinical Research Branch, National Institute on Aging, National Institutes of Health
Jeanette Erdmann: Medizinische Klinik II, Universität zu Lübeck
Paul Elliott: Imperial College London, St Mary’s Campus, Norfolk Place, London W2 1PG, UK.
Kenechi G. Ejebe: Broad Institute
Angela Döring: Institute of Epidemiology, Helmholtz Zentrum Munchen – German Research Center for Environmental Health
Anna F. Dominiczak: BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK.
Serkalem Demissie: Boston University School of Public Health
Panagiotis Deloukas: Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
Eco J. C. de Geus: VU University Amsterdam, Van der Boechorststraat 1, 1081 BT Amsterdam, The Netherlands.
Ulf de Faire: Institute of Environmental Medicine, Karolinska Institutet
Gabriel Crawford: Broad Institute
Francis S. Collins: National Human Genome Research Institute, National Institutes of Health
Yii- der I. Chen: Medical Genetics Institute, Cedars-Sinai Medical Center
Mark J. Caulfield: Clinical Pharmacology and Barts and the London Genome Centre, William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London
Harry Campbell: Centre for Population Health Sciences, University of Edinburgh
Noel P. Burtt: Broad Institute
Lori L. Bonnycastle: National Human Genome Research Institute, National Institutes of Health
Dorret I. Boomsma: VU University Amsterdam, Van der Boechorststraat 1, 1081 BT Amsterdam, The Netherlands.
S. Matthijs Boekholdt: Academic Medical Centre
Richard N. Bergman: University of Southern California
Inês Barroso: Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
Stefania Bandinelli: Geriatric Unit, Azienda Sanitaria Firenze (ASF)
Christie M. Ballantyne: Baylor College of Medicine
Themistocles L. Assimes: Stanford University School of Medicine
Thomas Quertermous: Stanford University School of Medicine
David Altshuler: Center for Human Genetic Research, Massachusetts General Hospital
Mark Seielstad: Genome Institute of Singapore
Tien Y. Wong: Singapore Eye Research Institute, National University of Singapore
E-Shyong Tai: Yong Loo Lin School of Medicine, National University of Singapore
Alan B. Feranil: Office of Population Studies Foundation, University of San Carlos
Christopher W. Kuzawa: Northwestern University
Linda S. Adair: Carolina Population Center, University of North Carolina
Herman A. Taylor: University of Mississippi Medical Center
Ingrid B. Borecki: Washington University School of Medicine
Stacey B. Gabriel: Broad Institute
James G. Wilson: University of Mississippi Medical Center
Hilma Holm: deCODE Genetics
Unnur Thorsteinsdottir: University of Iceland
Vilmundur Gudnason: Icelandic Heart Association, Heart Preventive Clinic and Research Institute
Ronald M. Krauss: Children’s Hospital Oakland Research Institute
Karen L. Mohlke: University of North Carolina
Jose M. Ordovas: Centro Nacional de Investigaciones Cardiovasculares
Patricia B. Munroe: Clinical Pharmacology and Barts and The London Genome Centre, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
Jaspal S. Kooner: Hammersmith Hospital, National Heart and Lung Institute, Imperial College London
Alan R. Tall: Columbia University
Robert A. Hegele: Robarts Research Institute, University of Western Ontario
John J.P. Kastelein: Academic Medical Centre at the University of Amsterdam
Eric E. Schadt: Sage Bionetworks
Jerome I. Rotter: Medical Genetics Institute, Cedars-Sinai Medical Center
Eric Boerwinkle: Human Genetics Center, University of Texas Health Science Center at Houston
David P. Strachan: St George’s University of London
Vincent Mooser: GlaxoSmithKline R&D
Kari Stefansson: University of Iceland
Muredach P. Reilly: Cardiovascular Institute, University of Pennsylvania School of Medicine
Nilesh J Samani: University of Leicester, NIHR Biomedical Research Unit in Cardiovascular Disease, Glenfield Hospital
Heribert Schunkert: Medizinische Klinik II, Universität zu Lübeck
L. Adrienne Cupples: Boston University School of Public Health
Manjinder S. Sandhu: Strangeways Research Laboratory, University of Cambridge
Paul M Ridker: Brigham and Women’s Hospital
Daniel J. Rader: Cardiovascular Institute, University of Pennsylvania School of Medicine
Cornelia M. van Duijn: Erasmus University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
Gonçalo R. Abecasis: Center for Statistical Genetics, University of Michigan
Michael Boehnke: Center for Statistical Genetics, University of Michigan
Sekar Kathiresan: Center for Human Genetic Research, Massachusetts General Hospital

Nature, 2010, vol. 466, issue 7307, 707-713

Abstract: Abstract Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P

Date: 2010
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