GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-12

AUTHORS

Nora Franceschini, Claudia Giambartolomei, Paul S. de Vries, Chris Finan, Joshua C. Bis, Rachael P. Huntley, Ruth C. Lovering, Salman M. Tajuddin, Thomas W. Winkler, Misa Graff, Maryam Kavousi, Caroline Dale, Albert V. Smith, Edith Hofer, Elisabeth M. van Leeuwen, Ilja M. Nolte, Lingyi Lu, Markus Scholz, Muralidharan Sargurupremraj, Niina Pitkänen, Oscar Franzén, Peter K. Joshi, Raymond Noordam, Riccardo E. Marioni, Shih-Jen Hwang, Solomon K. Musani, Ulf Schminke, Walter Palmas, Aaron Isaacs, Adolfo Correa, Alan B. Zonderman, Albert Hofman, Alexander Teumer, Amanda J. Cox, André G. Uitterlinden, Andrew Wong, Andries J. Smit, Anne B. Newman, Annie Britton, Arno Ruusalepp, Bengt Sennblad, Bo Hedblad, Bogdan Pasaniuc, Brenda W. Penninx, Carl D. Langefeld, Christina L. Wassel, Christophe Tzourio, Cristiano Fava, Damiano Baldassarre, Daniel H. O’Leary, Daniel Teupser, Diana Kuh, Elena Tremoli, Elmo Mannarino, Enzo Grossi, Eric Boerwinkle, Eric E. Schadt, Erik Ingelsson, Fabrizio Veglia, Fernando Rivadeneira, Frank Beutner, Ganesh Chauhan, Gerardo Heiss, Harold Snieder, Harry Campbell, Henry Völzke, Hugh S. Markus, Ian J. Deary, J. Wouter Jukema, Jacqueline de Graaf, Jacqueline Price, Janne Pott, Jemma C. Hopewell, Jingjing Liang, Joachim Thiery, Jorgen Engmann, Karl Gertow, Kenneth Rice, Kent D. Taylor, Klodian Dhana, Lambertus A. L. M. Kiemeney, Lars Lind, Laura M. Raffield, Lenore J. Launer, Lesca M. Holdt, Marcus Dörr, Martin Dichgans, Matthew Traylor, Matthias Sitzer, Meena Kumari, Mika Kivimaki, Mike A. Nalls, Olle Melander, Olli Raitakari, Oscar H. Franco, Oscar L. Rueda-Ochoa, Panos Roussos, Peter H. Whincup, Philippe Amouyel, Philippe Giral, Pramod Anugu, Quenna Wong, Rainer Malik, Rainer Rauramaa, Ralph Burkhardt, Rebecca Hardy, Reinhold Schmidt, Renée de Mutsert, Richard W. Morris, Rona J. Strawbridge, S. Goya Wannamethee, Sara Hägg, Sonia Shah, Stela McLachlan, Stella Trompet, Sudha Seshadri, Sudhir Kurl, Susan R. Heckbert, Susan Ring, Tamara B. Harris, Terho Lehtimäki, Tessel E. Galesloot, Tina Shah, Ulf de Faire, Vincent Plagnol, Wayne D. Rosamond, Wendy Post, Xiaofeng Zhu, Xiaoling Zhang, Xiuqing Guo, Yasaman Saba, , Abbas Dehghan, Adrie Seldenrijk, Alanna C. Morrison, Anders Hamsten, Bruce M. Psaty, Cornelia M. van Duijn, Deborah A. Lawlor, Dennis O. Mook-Kanamori, Donald W. Bowden, Helena Schmidt, James F. Wilson, James G. Wilson, Jerome I. Rotter, Joanna M. Wardlaw, John Deanfield, Julian Halcox, Leo-Pekka Lyytikäinen, Markus Loeffler, Michele K. Evans, Stéphanie Debette, Steve E. Humphries, Uwe Völker, Vilmundur Gudnason, Aroon D. Hingorani, Johan L. M. Björkegren, Juan P. Casas, Christopher J. O’Donnell

ABSTRACT

Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans. More... »

PAGES

5141

Journal

TITLE

Nature Communications

ISSUE

1

VOLUME

9

Author Affiliations

  • University of North Carolina System
  • University of California Los Angeles
  • The University of Texas Health Science Center at Houston
  • University College London
  • University of Washington
  • National Institute on Aging
  • University of Regensburg
  • Erasmus University Medical Center
  • University of Iceland
  • Medical University of Graz
  • University Medical Center Groningen
  • Wake Forest University
  • Leipzig University
  • University of Turku
  • Clinical Gene Networks (Sweden)
  • University of Edinburgh
  • Leiden University Medical Center
  • National Heart Lung and Blood Institute
  • University of Mississippi Medical Center
  • University of Greifswald
  • Columbia University
  • Maastricht University
  • German Centre for Cardiovascular Research
  • Griffith University
  • MRC Unit for Lifelong Health and Ageing
  • University of Pittsburgh
  • Tartu University Hospital
  • Uppsala University
  • Lund University
  • VU University Medical Center
  • University of Verona
  • Centro Cardiologico Monzino
  • St. Elizabeth's Medical Center
  • University of Milan
  • University of Perugia
  • Centro Diagnostico Italiano
  • Baylor College of Medicine
  • Stanford University
  • Indian Institute of Science Bangalore
  • University of Cambridge
  • Radboud University Nijmegen Medical Centre
  • University of Oxford
  • Case Western Reserve University
  • Karolinska Institute
  • Harbor–UCLA Medical Center
  • Rush University Medical Center
  • University of North Carolina at Chapel Hill
  • Munich Cluster for Systems Neurology
  • Goethe University Frankfurt
  • University of Essex
  • National Institutes of Health
  • Turku University Hospital
  • University of Bern
  • Industrial University of Santander
  • James J Peters VA Medical Center
  • Lille 1 University
  • Klinikum der Universität München
  • Kuopio University Hospital
  • University Hospital Regensburg
  • University of Bristol
  • University of Glasgow
  • Boston University School of Medicine
  • University of Eastern Finland
  • Kaiser Permanente Washington Health Research Institute
  • University of Tampere
  • Karolinska University Hospital
  • Johns Hopkins University
  • Boston University
  • Imperial College London
  • GGZ inGeest
  • Swansea University
  • University of Tartu
  • Harvard University
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41467-018-07340-5

    DOI

    http://dx.doi.org/10.1038/s41467-018-07340-5

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1110228479

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30510157


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