Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2011-10

AUTHORS

The International Consortium for Blood Pressure Genome-Wide Association Studies, Georg B. Ehret, Patricia B. Munroe, Kenneth M. Rice, Murielle Bochud, Andrew D. Johnson, Daniel I. Chasman, Albert V. Smith, Martin D. Tobin, Germaine C. Verwoert, Shih-Jen Hwang, Vasyl Pihur, Peter Vollenweider, Paul F. O’Reilly, Najaf Amin, Jennifer L. Bragg-Gresham, Alexander Teumer, Nicole L. Glazer, Lenore Launer, Jing Hua Zhao, Yurii Aulchenko, Simon Heath, Siim Sõber, Afshin Parsa, Jian’an Luan, Pankaj Arora, Abbas Dehghan, Feng Zhang, Gavin Lucas, Andrew A. Hicks, Anne U. Jackson, John F Peden, Toshiko Tanaka, Sarah H. Wild, Igor Rudan, Wilmar Igl, Yuri Milaneschi, Alex N. Parker, Cristiano Fava, John C. Chambers, Ervin R. Fox, Meena Kumari, Min Jin Go, Pim van der Harst, Wen Hong Linda Kao, Marketa Sjögren, D. G. Vinay, Myriam Alexander, Yasuharu Tabara, Sue Shaw-Hawkins, Peter H. Whincup, Yongmei Liu, Gang Shi, Johanna Kuusisto, Bamidele Tayo, Mark Seielstad, Xueling Sim, Khanh-Dung Hoang Nguyen, Terho Lehtimäki, Giuseppe Matullo, Ying Wu, Tom R. Gaunt, N. Charlotte Onland-Moret, Matthew N. Cooper, Carl G. P. Platou, Elin Org, Rebecca Hardy, Santosh Dahgam, Jutta Palmen, Veronique Vitart, Peter S. Braund, Tatiana Kuznetsova, Cuno S. P. M. Uiterwaal, Adebowale Adeyemo, Walter Palmas, Harry Campbell, Barbara Ludwig, Maciej Tomaszewski, Ioanna Tzoulaki, Nicholette D. Palmer, Thor Aspelund, Melissa Garcia, Yen-Pei C. Chang, Jeffrey R. O’Connell, Nanette I. Steinle, Diederick E. Grobbee, Dan E. Arking, Sharon L. Kardia, Alanna C. Morrison, Dena Hernandez, Samer Najjar, Wendy L. McArdle, David Hadley, Morris J. Brown, John M. Connell, Aroon D. Hingorani, Ian N.M. Day, Debbie A. Lawlor, John P. Beilby, Robert W. Lawrence, Robert Clarke, Jemma C. Hopewell, Halit Ongen, Albert W. Dreisbach, Yali Li, J. Hunter Young, Joshua C. Bis, Mika Kähönen, Jorma Viikari, Linda S. Adair, Nanette R. Lee, Ming-Huei Chen, Matthias Olden, Cristian Pattaro, Judith A. Hoffman Bolton, Anna Köttgen, Sven Bergmann, Vincent Mooser, Nish Chaturvedi, Timothy M. Frayling, Muhammad Islam, Tazeen H. Jafar, Jeanette Erdmann, Smita R. Kulkarni, Stefan R. Bornstein, Jürgen Grässler, Leif Groop, Benjamin F. Voight, Johannes Kettunen, Philip Howard, Andrew Taylor, Simonetta Guarrera, Fulvio Ricceri, Valur Emilsson, Andrew Plump, Inês Barroso, Kay-Tee Khaw, Alan B. Weder, Steven C. Hunt, Yan V. Sun, Richard N. Bergman, Francis S. Collins, Lori L. Bonnycastle, Laura J. Scott, Heather M. Stringham, Leena Peltonen, Markus Perola, Erkki Vartiainen, Stefan-Martin Brand, Jan A. Staessen, Thomas J. Wang, Paul R. Burton, Maria Soler Artigas, Yanbin Dong, Harold Snieder, Xiaoling Wang, Haidong Zhu, Kurt K. Lohman, Megan E. Rudock, Susan R. Heckbert, Nicholas L. Smith, Kerri L. Wiggins, Ayo Doumatey, Daniel Shriner, Gudrun Veldre, Margus Viigimaa, Sanjay Kinra, Dorairaj Prabhakaran, Vikal Tripathy, Carl D. Langefeld, Annika Rosengren, Dag S. Thelle, Anna Maria Corsi, Andrew Singleton, Terrence Forrester, Gina Hilton, Colin A. McKenzie, Tunde Salako, Naoharu Iwai, Yoshikuni Kita, Toshio Ogihara, Takayoshi Ohkubo, Tomonori Okamura, Hirotsugu Ueshima, Satoshi Umemura, Susana Eyheramendy, Thomas Meitinger, H.-Erich Wichmann, Yoon Shin Cho, Hyung-Lae Kim, Jong-Young Lee, James Scott, Joban S. Sehmi, Weihua Zhang, Bo Hedblad, Peter Nilsson, George Davey Smith, Andrew Wong, Narisu Narisu, Alena Stančáková, Leslie J. Raffel, Jie Yao, Sekar Kathiresan, Christopher J. O’Donnell, Stephen M. Schwartz, M. Arfan Ikram, W. T. Longstreth, Thomas H. Mosley, Sudha Seshadri, Nick R.G. Shrine, Louise V. Wain, Mario A. Morken, Amy J. Swift, Jaana Laitinen, Inga Prokopenko, Paavo Zitting, Jackie A. Cooper, Steve E. Humphries, John Danesh, Asif Rasheed, Anuj Goel, Anders Hamsten, Hugh Watkins, Stephan J. L. Bakker, Wiek H. van Gilst, Charles S. Janipalli, K. Radha Mani, Chittaranjan S. Yajnik, Albert Hofman, Francesco U. S. Mattace-Raso, Ben A. Oostra, Ayse Demirkan, Aaron Isaacs, Fernando Rivadeneira, Edward G. Lakatta, Marco Orru, Angelo Scuteri, Mika Ala-Korpela, Antti J. Kangas, Leo-Pekka Lyytikäinen, Pasi Soininen, Taru Tukiainen, Peter Würtz, Rick Twee-Hee Ong, Marcus Dörr, Heyo K. Kroemer, Uwe Völker, Henry Völzke, Pilar Galan, Serge Hercberg, Mark Lathrop, Diana Zelenika, Panos Deloukas, Massimo Mangino, Tim D. Spector, Guangju Zhai, James F. Meschia, Michael A. Nalls, Pankaj Sharma, Janos Terzic, M. V. Kranthi Kumar, Matthew Denniff, Ewa Zukowska-Szczechowska, Lynne E. Wagenknecht, F. Gerald R. Fowkes, Fadi J. Charchar, Peter E. H. Schwarz, Caroline Hayward, Xiuqing Guo, Charles Rotimi, Michiel L. Bots, Eva Brand, Nilesh J. Samani, Ozren Polasek, Philippa J. Talmud, Fredrik Nyberg, Diana Kuh, Maris Laan, Kristian Hveem, Lyle J. Palmer, Yvonne T. van der Schouw, Juan P. Casas, Karen L. Mohlke, Paolo Vineis, Olli Raitakari, Santhi K. Ganesh, Tien Y. Wong, E Shyong Tai, Richard S. Cooper, Markku Laakso, Dabeeru C. Rao, Tamara B. Harris, Richard W. Morris, Anna F. Dominiczak, Mika Kivimaki, Michael G. Marmot, Tetsuro Miki, Danish Saleheen, Giriraj R. Chandak, Josef Coresh, Gerjan Navis, Veikko Salomaa, Bok-Ghee Han, Xiaofeng Zhu, Jaspal S. Kooner, Olle Melander, Paul M Ridker, Stefania Bandinelli, Ulf B. Gyllensten, Alan F. Wright, James F. Wilson, Luigi Ferrucci, Martin Farrall, Jaakko Tuomilehto, Peter P. Pramstaller, Roberto Elosua, Nicole Soranzo, Eric J. G. Sijbrands, David Altshuler, Ruth J. F. Loos, Alan R. Shuldiner, Christian Gieger, Pierre Meneton, Andre G. Uitterlinden, Nicholas J. Wareham, Vilmundur Gudnason, Jerome I. Rotter, Rainer Rettig, Manuela Uda, David P. Strachan, Jacqueline C. M. Witteman, Anna-Liisa Hartikainen, Jacques S. Beckmann, Eric Boerwinkle, Ramachandran S. Vasan, Michael Boehnke, Martin G. Larson, Marjo-Riitta Järvelin, Bruce M. Psaty, Gonçalo R. Abecasis, Aravinda Chakravarti, Paul Elliott, Cornelia M. van Duijn, Christopher Newton-Cheh, Daniel Levy, Mark J. Caulfield, Toby Johnson

ABSTRACT

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention. More... »

PAGES

103

Journal

TITLE

Nature

ISSUE

7367

VOLUME

478

Author Affiliations

  • University Hospital of Geneva
  • Queen Mary University of London
  • University of Washington
  • Institute of Social and Preventive Medicine
  • National Heart Lung and Blood Institute
  • Harvard University
  • University of Iceland
  • University of Leicester
  • Netherlands Consortium for Healthy Ageing
  • Johns Hopkins University
  • University Hospital of Lausanne
  • Imperial College London
  • Erasmus University Medical Center
  • University of Michigan–Ann Arbor
  • University of Greifswald
  • National Institutes of Health
  • Centre National de Génotypage
  • University of Tartu
  • University of Maryland, Baltimore
  • Massachusetts General Hospital
  • King's College London
  • Pompeu Fabra University
  • University of Lübeck
  • Wellcome Centre for Human Genetics
  • National Institute on Aging
  • University of Edinburgh
  • University of Split
  • Uppsala University
  • Amgen (United States)
  • University of Verona
  • Ealing Hospital
  • University of Mississippi Medical Center
  • University College London
  • Korea National Institute of Health
  • Lund University
  • Centre for Cellular and Molecular Biology
  • University of Cambridge
  • Ehime University
  • St George's, University of London
  • Wake Forest University
  • Washington University in St. Louis
  • Loyola University Chicago
  • Genome Institute of Singapore
  • National University of Singapore
  • University of Tampere
  • Human Genetics Foundation
  • University of North Carolina at Chapel Hill
  • University of Bristol
  • University Medical Center Utrecht
  • University of Western Australia
  • Norwegian University of Science and Technology
  • MRC Unit for Lifelong Health and Ageing
  • University of Gothenburg
  • Medical Research Council Institute of Genetics and Molecular Medicine
  • Glenfield Hospital
  • KU Leuven
  • National Human Genome Research Institute
  • Columbia University
  • TU Dresden
  • University of Ioannina
  • Wake Forest Baptist Medical Center
  • The University of Texas Health Science Center at Houston
  • MedStar Washington Hospital Center
  • University of South Florida
  • Pathwest Laboratory Medicine
  • University of Oxford
  • Case Western Reserve University
  • Tampere University Hospital
  • Turku University Hospital
  • University of North Carolina System
  • University of San Carlos
  • Boston University School of Medicine
  • University Hospital Regensburg
  • Swiss Institute of Bioinformatics
  • GlaxoSmithKline (United States)
  • University of Exeter
  • Aga Khan University
  • King Edward Memorial Hospital Research Centre
  • Broad Institute
  • Institute for Molecular Medicine Finland
  • MSD (United States)
  • University of Utah
  • University of Southern California
  • National Institute for Health and Welfare
  • University of Münster
  • Augusta University
  • Group Health Cooperative
  • North Estonia Medical Centre
  • Public Health Foundation of India
  • University of Oslo
  • University of the West Indies
  • University of Ibadan
  • Shiga University of Medical Science
  • Osaka University
  • Tohoku University
  • Yokohama City University
  • Pontifical Catholic University of Chile
  • University of Bonn
  • Klinikum der Universität München
  • Cedars-Sinai Medical Center
  • Finnish Institute of Occupational Health
  • Lapland Central Hospital
  • Karolinska Institute
  • Ospedaliero Santa Barbara
  • University of Oulu
  • University of Eastern Finland
  • Aalto University
  • University of Helsinki
  • Paris 13 University
  • Wellcome Sanger Institute
  • Mayo Clinic
  • Medical University of Silesia
  • Federation University
  • University Hospital Münster
  • University of Zagreb
  • AstraZeneca (Sweden)
  • University of Toronto
  • London School of Hygiene & Tropical Medicine
  • Michigan Medicine
  • Duke NUS Graduate Medical School
  • University of Glasgow
  • Brigham and Women's Hospital
  • Azienda Sanitaria di Firenze
  • Hospital Universitario La Paz
  • Ospedale di Bolzano
  • Instituto de Salud Carlos III
  • Baltimore VA Medical Center
  • Friedrich Loeffler Institute
  • Centre de Recherche des Cordeliers
  • University of Cagliari
  • Boston University
  • Centre for Medical Systems Biology
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nature10405

    DOI

    http://dx.doi.org/10.1038/nature10405

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1000059117

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/21909115


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