The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-10

AUTHORS

Georg B Ehret, Teresa Ferreira, Daniel I Chasman, Anne U Jackson, Ellen M Schmidt, Toby Johnson, Gudmar Thorleifsson, Jian'an Luan, Louise A Donnelly, Stavroula Kanoni, Ann-Kristin Petersen, Vasyl Pihur, Rona J Strawbridge, Dmitry Shungin, Maria F Hughes, Osorio Meirelles, Marika Kaakinen, Nabila Bouatia-Naji, Kati Kristiansson, Sonia Shah, Marcus E Kleber, Xiuqing Guo, Leo-Pekka Lyytikäinen, Cristiano Fava, Niclas Eriksson, Ilja M Nolte, Patrik K Magnusson, Elias L Salfati, Loukianos S Rallidis, Elizabeth Theusch, Andrew J P Smith, Lasse Folkersen, Kate Witkowska, Tune H Pers, Roby Joehanes, Stuart K Kim, Lazaros Lataniotis, Rick Jansen, Andrew D Johnson, Helen Warren, Young Jin Kim, Wei Zhao, Ying Wu, Bamidele O Tayo, Murielle Bochud, CHARGE-EchoGen Consortium, CHARGE-HF Consortium, Wellcome Trust Case Control Consortium, Devin Absher, Linda S Adair, Najaf Amin, Dan E Arking, Tomas Axelsson, Damiano Baldassarre, Beverley Balkau, Stefania Bandinelli, Michael R Barnes, Inês Barroso, Stephen Bevan, Joshua C Bis, Gyda Bjornsdottir, Michael Boehnke, Eric Boerwinkle, Lori L Bonnycastle, Dorret I Boomsma, Stefan R Bornstein, Morris J Brown, Michel Burnier, Claudia P Cabrera, John C Chambers, I-Shou Chang, Ching-Yu Cheng, Peter S Chines, Ren-Hua Chung, Francis S Collins, John M Connell, Angela Döring, Jean Dallongeville, John Danesh, Ulf de Faire, Graciela Delgado, Anna F Dominiczak, Alex S F Doney, Fotios Drenos, Sarah Edkins, John D Eicher, Roberto Elosua, Stefan Enroth, Jeanette Erdmann, Per Eriksson, Tonu Esko, Evangelos Evangelou, Alun Evans, Tove Fall, Martin Farrall, Janine F Felix, Jean Ferrières, Luigi Ferrucci, Myriam Fornage, Terrence Forrester, Nora Franceschini, Oscar H Franco, Anders Franco-Cereceda, Ross M Fraser, Santhi K Ganesh, He Gao, Karl Gertow, Francesco Gianfagna, Bruna Gigante, Franco Giulianini, Anuj Goel, Alison H Goodall, Mark O Goodarzi, Mathias Gorski, Jürgen Gräßler, Christopher J Groves, Vilmundur Gudnason, Ulf Gyllensten, Göran Hallmans, Anna-Liisa Hartikainen, Maija Hassinen, Aki S Havulinna, Caroline Hayward, Serge Hercberg, Karl-Heinz Herzig, Andrew A Hicks, Aroon D Hingorani, Joel N Hirschhorn, Albert Hofman, Jostein Holmen, Oddgeir Lingaas Holmen, Jouke-Jan Hottenga, Phil Howard, Chao A Hsiung, Steven C Hunt, M Arfan Ikram, Thomas Illig, Carlos Iribarren, Richard A Jensen, Mika Kähönen, Hyun Min Kang, Sekar Kathiresan, Brendan J Keating, Kay-Tee Khaw, Yun Kyoung Kim, Eric Kim, Mika Kivimaki, Norman Klopp, Genovefa Kolovou, Pirjo Komulainen, Jaspal S Kooner, Gulum Kosova, Ronald M Krauss, Diana Kuh, Zoltan Kutalik, Johanna Kuusisto, Kirsti Kvaløy, Timo A Lakka, Nanette R Lee, I-Te Lee, Wen-Jane Lee, Daniel Levy, Xiaohui Li, Kae-Woei Liang, Honghuang Lin, Li Lin, Jaana Lindström, Stéphane Lobbens, Satu Männistö, Gabriele Müller, Martina Müller-Nurasyid, François Mach, Hugh S Markus, Eirini Marouli, Mark I McCarthy, Colin A McKenzie, Pierre Meneton, Cristina Menni, Andres Metspalu, Vladan Mijatovic, Leena Moilanen, May E Montasser, Andrew D Morris, Alanna C Morrison, Antonella Mulas, Ramaiah Nagaraja, Narisu Narisu, Kjell Nikus, Christopher J O'Donnell, Paul F O'Reilly, Ken K Ong, Fred Paccaud, Cameron D Palmer, Afshin Parsa, Nancy L Pedersen, Brenda W Penninx, Markus Perola, Annette Peters, Neil Poulter, Peter P Pramstaller, Bruce M Psaty, Thomas Quertermous, Dabeeru C Rao, Asif Rasheed, N William Rayner, Frida Renström, Rainer Rettig, Kenneth M Rice, Robert Roberts, Lynda M Rose, Jacques Rossouw, Nilesh J Samani, Serena Sanna, Jouko Saramies, Heribert Schunkert, Sylvain Sebert, Wayne H-H Sheu, Young-Ah Shin, Xueling Sim, Johannes H Smit, Albert V Smith, Maria X Sosa, Tim D Spector, Alena Stančáková, Alice V Stanton, Kathleen E Stirrups, Heather M Stringham, Johan Sundstrom, Amy J Swift, Ann-Christine Syvänen, E-Shyong Tai, Toshiko Tanaka, Kirill V Tarasov, Alexander Teumer, Unnur Thorsteinsdottir, Martin D Tobin, Elena Tremoli, Andre G Uitterlinden, Matti Uusitupa, Ahmad Vaez, Dhananjay Vaidya, Cornelia M van Duijn, Erik P A van Iperen, Ramachandran S Vasan, Germaine C Verwoert, Jarmo Virtamo, Veronique Vitart, Benjamin F Voight, Peter Vollenweider, Aline Wagner, Louise V Wain, Nicholas J Wareham, Hugh Watkins, Alan B Weder, Harm-Jan Westra, Rainford Wilks, Tom Wilsgaard, James F Wilson, Tien Y Wong, Tsun-Po Yang, Jie Yao, Loic Yengo, Weihua Zhang, Jing Hua Zhao, Xiaofeng Zhu, Pascal Bovet, Richard S Cooper, Karen L Mohlke, Danish Saleheen, Jong-Young Lee, Paul Elliott, Hinco J Gierman, Cristen J Willer, Lude Franke, G Kees Hovingh, Kent D Taylor, George Dedoussis, Peter Sever, Andrew Wong, Lars Lind, Themistocles L Assimes, Inger Njølstad, Peter E H Schwarz, Claudia Langenberg, Harold Snieder, Mark J Caulfield, Olle Melander, Markku Laakso, Juha Saltevo, Rainer Rauramaa, Jaakko Tuomilehto, Erik Ingelsson, Terho Lehtimäki, Kristian Hveem, Walter Palmas, Winfried März, Meena Kumari, Veikko Salomaa, Yii-Der I Chen, Jerome I Rotter, Philippe Froguel, Marjo-Riitta Jarvelin, Edward G Lakatta, Kari Kuulasmaa, Paul W Franks, Anders Hamsten, H-Erich Wichmann, Colin N A Palmer, Kari Stefansson, Paul M Ridker, Ruth J F Loos, Aravinda Chakravarti, Panos Deloukas, Andrew P Morris, Christopher Newton-Cheh, Patricia B Munroe

ABSTRACT

To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure-associated loci, of which 17 were new; 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target organ damage in multiple tissues but with minor effects in the kidney. Our findings expand current knowledge of blood pressure-related pathways and highlight tissues beyond the classical renal system in blood pressure regulation. More... »

PAGES

1171-1184

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  • Journal

    TITLE

    Nature Genetics

    ISSUE

    10

    VOLUME

    48

    Author Affiliations

  • University Hospital of Geneva
  • Wellcome Centre for Human Genetics
  • Harvard University
  • University of Michigan–Ann Arbor
  • GlaxoSmithKline (United Kingdom)
  • Institute of Metabolic Science
  • Queen Mary University of London
  • Helmholtz Zentrum München
  • Johns Hopkins University
  • Karolinska University Hospital
  • Umeå University
  • Queen's University Belfast
  • National Institute on Aging
  • Imperial College London
  • Paris Descartes University
  • University of Helsinki
  • University College London
  • Heidelberg University
  • University of California Los Angeles
  • University of Tampere
  • University of Verona
  • Uppsala University
  • University Medical Center Groningen
  • Karolinska Institute
  • Stanford University
  • National and Kapodistrian University of Athens
  • UCSF Benioff Children's Hospital
  • Statens Serum Institut
  • National Heart Lung and Blood Institute
  • Stanford Medicine
  • VU University Medical Center
  • Korea National Institute of Health
  • University of Pennsylvania
  • University of North Carolina at Chapel Hill
  • Loyola University Chicago
  • Institute of Social and Preventive Medicine
  • HudsonAlpha Institute for Biotechnology
  • Erasmus University Medical Center
  • Centro Cardiologico Monzino
  • Centre for research in epidemiology and population health
  • Azienda Sanitaria di Firenze
  • University of Lincoln
  • University of Washington
  • The University of Texas Health Science Center at Houston
  • National Human Genome Research Institute
  • VU University Amsterdam
  • TU Dresden
  • University of Lausanne
  • Imperial College Healthcare NHS Trust
  • National Health Research Institutes
  • Duke NUS Graduate Medical School
  • University of Cambridge
  • University of Glasgow
  • University of Bristol
  • Wellcome Sanger Institute
  • Institut Hospital del Mar d'Investigacions Mèdiques
  • University of Lübeck
  • Broad Institute
  • University of Ioannina
  • University of Oxford
  • Hôpital Rangueil
  • University of the West Indies
  • University of Edinburgh
  • Istituto Neurologico Mediterraneo
  • Brigham and Women's Hospital
  • Glenfield Hospital
  • Cedars-Sinai Medical Center
  • University Hospital Regensburg
  • University of Iceland
  • Oulu University Hospital
  • Kuopion Liikuntalääketieteen Tutkimuslaitos
  • National Institute for Health and Welfare
  • Western General Hospital
  • Nutritional Epidemiology Research Unit
  • Poznan University of Medical Sciences
  • European Academy of Bozen
  • Norwegian University of Science and Technology
  • St Olav's University Hospital
  • Weill Cornell Medical College in Qatar
  • Hannover Medical School
  • Kaiser Permanente
  • Massachusetts General Hospital
  • Onassis Cardiac Surgery Center
  • MRC Unit for Lifelong Health and Ageing
  • Swiss Institute of Bioinformatics
  • Kuopio University Hospital
  • University of San Carlos
  • National Yang Ming University
  • Taichung Veterans General Hospital
  • Boston University School of Medicine
  • Université Lille 2 Droit et Santé
  • Ludwig Maximilian University of Munich
  • Harokopio University
  • Sorbonne University
  • King's College London
  • University of Tartu
  • University of Maryland, Baltimore
  • Institute of Genetic and Biomedical Research
  • Boston Children's Hospital
  • Leiden University Medical Center
  • Group Health Cooperative
  • Washington University in St. Louis
  • Center for Non-Communicable Diseases
  • University of Greifswald
  • University of Ottawa
  • South Karelia Central Hospital
  • Technical University Munich
  • University of Oulu
  • National Defense Medical Center
  • EMGO Institute for Health and Care Research
  • Royal College of Surgeons in Ireland
  • University of Leicester
  • Isfahan University of Medical Sciences
  • Centre for Medical Systems Biology
  • Academic Medical Center
  • University Hospital of Lausanne
  • University of Strasbourg
  • The Arctic University of Norway
  • Ealing Hospital NHS Trust
  • Case Western Reserve University
  • Ministry of Health
  • Illumina (United States)
  • German Center for Diabetes Research
  • Lund University
  • Central Finland Health Care District
  • Danube University Krems
  • Columbia University
  • Medical University of Graz
  • Icahn School of Medicine at Mount Sinai
  • King Abdulaziz University
  • University of Liverpool
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ng.3667

    DOI

    http://dx.doi.org/10.1038/ng.3667

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1007132667

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/27618452


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