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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2010-08

AUTHORS

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, Maisa 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, Kari Stefansson, 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, Hilma Holm, 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, Sekar Kathiresan

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 < 5 x 10(-8)), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD. More... »

PAGES

707

Journal

TITLE

Nature

ISSUE

7307

VOLUME

466

Author Affiliations

  • University of Michigan–Ann Arbor
  • Johns Hopkins University
  • University of Iceland
  • University of Pennsylvania
  • Columbia University
  • National Institute for Health and Welfare
  • Brigham and Women's Hospital
  • Western University
  • Academic Medical Center
  • Erasmus University Medical Center
  • National Heart Lung and Blood Institute
  • The University of Texas Health Science Center at Houston
  • University of Cambridge
  • University of Washington
  • deCODE Genetics (Iceland)
  • Washington University in St. Louis
  • Imperial College London
  • Lund University
  • Queen Mary University of London
  • Cedars-Sinai Medical Center
  • Korea National Institute of Health
  • Seoul National University
  • Sookmyung Women's University
  • National University of Singapore
  • Genome Institute of Singapore
  • University of North Carolina at Chapel Hill
  • GlaxoSmithKline (United States)
  • Innsbruck Medical University
  • University of Lübeck
  • Medical Research Council Institute of Genetics and Molecular Medicine
  • Wageningen University & Research
  • University of Edinburgh
  • VU University Amsterdam
  • QIMR Berghofer Medical Research Institute
  • University Hospital of Lausanne
  • Broad Institute
  • University of Cagliari
  • University of Leicester
  • MedStar Health
  • King's College London
  • Wellcome Sanger Institute
  • Helsinki University Central Hospital
  • Istituti di Ricovero e Cura a Carattere Scientifico
  • National Institute on Aging
  • Institute for Molecular Medicine Finland
  • University of California Los Angeles
  • University of Oulu
  • University of Ottawa
  • Karolinska Institute
  • Amgen (United States)
  • McMaster University
  • Churchill Hospital
  • University of Bristol
  • Istituto di Genomica Applicata
  • Pompeu Fabra University
  • National Institutes of Health
  • Tampere University Hospital
  • University of Southern Denmark
  • University of Helsinki
  • Massachusetts General Hospital
  • Uppsala University
  • University of Regensburg
  • Aalto University
  • University of Leeds
  • University of Glasgow
  • National Human Genome Research Institute
  • University of Southern California
  • Azienda Sanitaria di Firenze
  • Baylor College of Medicine
  • Stanford University
  • University of San Carlos
  • Northwestern University
  • University of Mississippi Medical Center
  • UCSF Benioff Children's Hospital
  • Sage Bionetworks
  • University College London
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nature09270

    DOI

    http://dx.doi.org/10.1038/nature09270

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1050402786

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/20686565


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