Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-10

AUTHORS

Praveen Surendran, Fotios Drenos, Robin Young, Helen Warren, James P Cook, Alisa K Manning, Niels Grarup, Xueling Sim, Daniel R Barnes, Kate Witkowska, James R Staley, Vinicius Tragante, Taru Tukiainen, Hanieh Yaghootkar, Nicholas Masca, Daniel F Freitag, Teresa Ferreira, Olga Giannakopoulou, Andrew Tinker, Magdalena Harakalova, Evelin Mihailov, Chunyu Liu, Aldi T Kraja, Sune Fallgaard Nielsen, Asif Rasheed, Maria Samuel, Wei Zhao, Lori L Bonnycastle, Anne U Jackson, Narisu Narisu, Amy J Swift, Lorraine Southam, Jonathan Marten, Jeroen R Huyghe, Alena Stančáková, Cristiano Fava, Therese Ohlsson, Angela Matchan, Kathleen E Stirrups, Jette Bork-Jensen, Anette P Gjesing, Jukka Kontto, Markus Perola, Susan Shaw-Hawkins, Aki S Havulinna, He Zhang, Louise A Donnelly, Christopher J Groves, N William Rayner, Matt J Neville, Neil R Robertson, Andrianos M Yiorkas, Karl-Heinz Herzig, Eero Kajantie, Weihua Zhang, Sara M Willems, Lars Lannfelt, Giovanni Malerba, Nicole Soranzo, Elisabetta Trabetti, Niek Verweij, Evangelos Evangelou, Alireza Moayyeri, Anne-Claire Vergnaud, Christopher P Nelson, Alaitz Poveda, Tibor V Varga, Muriel Caslake, Anton JM de Craen, Stella Trompet, Jian’an Luan, Robert A Scott, Sarah E Harris, David CM Liewald, Riccardo Marioni, Cristina Menni, Aliki-Eleni Farmaki, Göran Hallmans, Frida Renström, Jennifer E Huffman, Maija Hassinen, Stephen Burgess, Ramachandran S Vasan, Janine F Felix, , Maria Uria-Nickelsen, Anders Malarstig, Dermot F Reily, Maarten Hoek, Thomas Vogt, Honghuang Lin, Wolfgang Lieb, , Matthew Traylor, Hugh F Markus, , Heather M Highland, Anne E Justice, Eirini Marouli, , Jaana Lindström, Matti Uusitupa, Pirjo Komulainen, Timo A Lakka, Rainer Rauramaa, Ozren Polasek, Igor Rudan, Olov Rolandsson, Paul W Franks, George Dedoussis, Timothy D Spector, , Pekka Jousilahti, Satu Männistö, Ian J Deary, John M Starr, Claudia Langenberg, Nick J Wareham, Morris J Brown, Anna F Dominiczak, John M Connell, J Wouter Jukema, Naveed Sattar, Ian Ford, Chris J Packard, Tõnu Esko, Reedik Mägi, Andres Metspalu, Rudolf A de Boer, Peter van der Meer, Pim van der Harst, , Giovanni Gambaro, Erik Ingelsson, Lars Lind, Paul IW de Bakker, Mattijs E Numans, Ivan Brandslund, Cramer Christensen, Eva RB Petersen, Eeva Korpi-Hyövälti, Heikki Oksa, John C Chambers, Jaspal S Kooner, Alexandra IF Blakemore, Steve Franks, Marjo-Riitta Jarvelin, Lise L Husemoen, Allan Linneberg, Tea Skaaby, Betina Thuesen, Fredrik Karpe, Jaakko Tuomilehto, Alex SF Doney, Andrew D Morris, Colin NA Palmer, Oddgeir Lingaas Holmen, Kristian Hveem, Cristen J Willer, Tiinamaija Tuomi, Leif Groop, AnneMari Käräjämäki, Aarno Palotie, Samuli Ripatti, Veikko Salomaa, Dewan S Alam, Abdulla al Shafi Majumder, Emanuele Di Angelantonio, Rajiv Chowdhury, Mark I McCarthy, Neil Poulter, Alice V Stanton, Peter Sever, Philippe Amouyel, Dominique Arveiler, Stefan Blankenberg, Jean Ferrières, Frank Kee, Kari Kuulasmaa, Martina Müller-Nurasyid, Giovanni Veronesi, Jarmo Virtamo, Panos Deloukas, , Paul Elliott, , Eleftheria Zeggini, Sekar Kathiresan, Olle Melander, Johanna Kuusisto, Markku Laakso, Sandosh Padmanabhan, David Porteous, Caroline Hayward, Generation Scotland, Francis S Collins, Karen L Mohlke, Torben Hansen, Oluf Pedersen, Michael Boehnke, Heather M Stringham, , Philippe Frossard, Christopher Newton-Cheh, , Martin D Tobin, Børge Grønne Nordestgaard, , , , , Mark J Caulfield, Anubha Mahajan, Andrew P Morris, Maciej Tomaszewski, Nilesh J Samani, Danish Saleheen, Folkert W Asselbergs, Cecilia M Lindgren, John Danesh, Louise V Wain, Adam S Butterworth, Joanna MM Howson, Patricia B Munroe

ABSTRACT

High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to 192,763 individuals and used ∼155,063 samples for independent replication. We identified 30 new blood pressure- or hypertension-associated genetic regions in the general population, including 3 rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5 mm Hg/allele) than common variants. Multiple rare nonsense and missense variant associations were found in A2ML1, and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention. More... »

PAGES

1151-1161

References to SciGraph publications

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  • Journal

    TITLE

    Nature Genetics

    ISSUE

    10

    VOLUME

    48

    Author Affiliations

  • University of Cambridge
  • University College London
  • Queen Mary University of London
  • University of Liverpool
  • Massachusetts General Hospital
  • University of Copenhagen
  • National University of Singapore
  • University Medical Center Utrecht
  • University of Exeter
  • University of Leicester
  • Wellcome Centre for Human Genetics
  • University of Tartu
  • National Heart Lung and Blood Institute
  • Washington University in St. Louis
  • University of Pennsylvania
  • National Human Genome Research Institute
  • University of Michigan–Ann Arbor
  • University of Edinburgh
  • University of Verona
  • Lund University
  • Wellcome Sanger Institute
  • National Institute for Health and Welfare
  • University of Oxford
  • NIHR Oxford Musculoskeletal Biomedical Research Unit
  • Brunel University London
  • Poznan University of Medical Sciences
  • University of Oulu
  • Ealing Hospital
  • Uppsala University
  • University of Ioannina
  • Imperial College London
  • University of the Basque Country
  • University of Glasgow
  • Leiden University Medical Center
  • University of Queensland
  • King's College London
  • Harokopio University
  • Umeå University
  • Kuopion Liikuntalääketieteen Tutkimuslaitos
  • Boston University
  • Erasmus University Medical Center
  • MSD (United States)
  • Boston University School of Medicine
  • Kiel University
  • University of North Carolina at Chapel Hill
  • Kuopio University Hospital
  • University of Split
  • Harvard University
  • Netherlands Heart Institute
  • Broad Institute
  • University Medical Center Groningen
  • Catholic University of the Sacred Heart
  • Stanford University
  • University of Southern Denmark
  • Sygehus Lillebælt
  • Seinäjoen Keskussairaala
  • Tampere University Hospital
  • Imperial College Healthcare NHS Trust
  • Oulu University Hospital
  • King Abdulaziz University
  • St Olav's University Hospital
  • Levanger Hospital
  • Institute for Molecular Medicine Finland
  • Vaasa Central Hospital
  • International Centre for Diarrhoeal Disease Research
  • National Institute of Cardiovascular Diseases
  • Royal College of Surgeons in Ireland
  • Pasteur Institute of Lille
  • University of Strasbourg
  • University Medical Center Hamburg-Eppendorf
  • Centre Hospitalier Universitaire de Toulouse
  • German Centre for Cardiovascular Research
  • University of Insubria
  • University of Manchester
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ng.3654

    DOI

    http://dx.doi.org/10.1038/ng.3654

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1044515196

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/27618447


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