Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-04

AUTHORS

Rainer Malik, Ganesh Chauhan, Matthew Traylor, Muralidharan Sargurupremraj, Yukinori Okada, Aniket Mishra, Loes Rutten-Jacobs, Anne-Katrin Giese, Sander W. van der Laan, Solveig Gretarsdottir, Christopher D. Anderson, Michael Chong, Hieab H. H. Adams, Tetsuro Ago, Peter Almgren, Philippe Amouyel, Hakan Ay, Traci M. Bartz, Oscar R. Benavente, Steve Bevan, Giorgio B. Boncoraglio, Robert D. Brown, Adam S. Butterworth, Caty Carrera, Cara L. Carty, Daniel I. Chasman, Wei-Min Chen, John W. Cole, Adolfo Correa, Ioana Cotlarciuc, Carlos Cruchaga, John Danesh, Paul I. W. de Bakker, Anita L. DeStefano, Marcel den Hoed, Qing Duan, Stefan T. Engelter, Guido J. Falcone, Rebecca F. Gottesman, Raji P. Grewal, Vilmundur Gudnason, Stefan Gustafsson, Jeffrey Haessler, Tamara B. Harris, Ahamad Hassan, Aki S. Havulinna, Susan R. Heckbert, Elizabeth G. Holliday, George Howard, Fang-Chi Hsu, Hyacinth I. Hyacinth, M. Arfan Ikram, Erik Ingelsson, Marguerite R. Irvin, Xueqiu Jian, Jordi Jiménez-Conde, Julie A. Johnson, J. Wouter Jukema, Masahiro Kanai, Keith L. Keene, Brett M. Kissela, Dawn O. Kleindorfer, Charles Kooperberg, Michiaki Kubo, Leslie A. Lange, Carl D. Langefeld, Claudia Langenberg, Lenore J. Launer, Jin-Moo Lee, Robin Lemmens, Didier Leys, Cathryn M. Lewis, Wei-Yu Lin, Arne G. Lindgren, Erik Lorentzen, Patrik K. Magnusson, Jane Maguire, Ani Manichaikul, Patrick F. McArdle, James F. Meschia, Braxton D. Mitchell, Thomas H. Mosley, Michael A. Nalls, Toshiharu Ninomiya, Martin J. O’Donnell, Bruce M. Psaty, Sara L. Pulit, Kristiina Rannikmäe, Alexander P. Reiner, Kathryn M. Rexrode, Kenneth Rice, Stephen S. Rich, Paul M. Ridker, Natalia S. Rost, Peter M. Rothwell, Jerome I. Rotter, Tatjana Rundek, Ralph L. Sacco, Saori Sakaue, Michele M. Sale, Veikko Salomaa, Bishwa R. Sapkota, Reinhold Schmidt, Carsten O. Schmidt, Ulf Schminke, Pankaj Sharma, Agnieszka Slowik, Cathie L. M. Sudlow, Christian Tanislav, Turgut Tatlisumak, Kent D. Taylor, Vincent N. S. Thijs, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Steffen Tiedt, Stella Trompet, Christophe Tzourio, Cornelia M. van Duijn, Matthew Walters, Nicholas J. Wareham, Sylvia Wassertheil-Smoller, James G. Wilson, Kerri L. Wiggins, Qiong Yang, Salim Yusuf, Joshua C. Bis, Tomi Pastinen, Arno Ruusalepp, Eric E. Schadt, Simon Koplev, Johan L. M. Björkegren, Veronica Codoni, Mete Civelek, Nicholas L. Smith, David A. Trégouët, Ingrid E. Christophersen, Carolina Roselli, Steven A. Lubitz, Patrick T. Ellinor, E. Shyong Tai, Jaspal S. Kooner, Norihiro Kato, Jiang He, Pim van der Harst, Paul Elliott, John C. Chambers, Fumihiko Takeuchi, Andrew D. Johnson, Dharambir K. Sanghera, Olle Melander, Christina Jern, Daniel Strbian, Israel Fernandez-Cadenas, W. T. Longstreth, Arndt Rolfs, Jun Hata, Daniel Woo, Jonathan Rosand, Guillaume Pare, Jemma C. Hopewell, Danish Saleheen, Kari Stefansson, Bradford B. Worrall, Steven J. Kittner, Sudha Seshadri, Myriam Fornage, Hugh S. Markus, Joanna M. M. Howson, Yoichiro Kamatani, Stephanie Debette, Martin Dichgans, Rainer Malik, Ganesh Chauhan, Matthew Traylor, Muralidharan Sargurupremraj, Yukinori Okada, Aniket Mishra, Loes Rutten-Jacobs, Anne-Katrin Giese, Sander W. van der Laan, Solveig Gretarsdottir, Christopher D. Anderson, Michael Chong, Hieab H. H. Adams, Tetsuro Ago, Peter Almgren, Philippe Amouyel, Hakan Ay, Traci M. Bartz, Oscar R. Benavente, Steve Bevan, Giorgio B. Boncoraglio, Robert D. Brown, Adam S. Butterworth, Caty Carrera, Cara L. Carty, Daniel I. Chasman, Wei-Min Chen, John W. Cole, Adolfo Correa, Ioana Cotlarciuc, Carlos Cruchaga, John Danesh, Paul I. W. de Bakker, Anita L. DeStefano, Marcel den Hoed, Qing Duan, Stefan T. Engelter, Guido J. Falcone, Rebecca F. Gottesman, Raji P. Grewal, Vilmundur Gudnason, Stefan Gustafsson, Jeffrey Haessler, Tamara B. Harris, Ahamad Hassan, Aki S. Havulinna, Susan R. Heckbert, Elizabeth G. Holliday, George Howard, Fang-Chi Hsu, Hyacinth I. Hyacinth, M. Arfan Ikram, Erik Ingelsson, Marguerite R. Irvin, Xueqiu Jian, Jordi Jiménez-Conde, Julie A. Johnson, J. Wouter Jukema, Masahiro Kanai, Keith L. Keene, Brett M. Kissela, Dawn O. Kleindorfer, Charles Kooperberg, Michiaki Kubo, Leslie A. Lange, Carl D. Langefeld, Claudia Langenberg, Lenore J. Launer, Jin-Moo Lee, Robin Lemmens, Didier Leys, Cathryn M. Lewis, Wei-Yu Lin, Arne G. Lindgren, Erik Lorentzen, Patrik K. Magnusson, Jane Maguire, Ani Manichaikul, Patrick F. McArdle, James F. Meschia, Braxton D. Mitchell, Thomas H. Mosley, Michael A. Nalls, Toshiharu Ninomiya, Martin J. O’Donnell, Bruce M. Psaty, Sara L. Pulit, Kristiina Rannikmäe, Alexander P. Reiner, Kathryn M. Rexrode, Kenneth Rice, Stephen S. Rich, Paul M. Ridker, Natalia S. Rost, Peter M. Rothwell, Jerome I. Rotter, Tatjana Rundek, Ralph L. Sacco, Saori Sakaue, Michele M. Sale, Veikko Salomaa, Bishwa R. Sapkota, Reinhold Schmidt, Carsten O. Schmidt, Ulf Schminke, Pankaj Sharma, Agnieszka Slowik, Cathie L. M. Sudlow, Christian Tanislav, Turgut Tatlisumak, Kent D. Taylor, Vincent N. S. Thijs, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Steffen Tiedt, Stella Trompet, Christophe Tzourio, Cornelia M. van Duijn, Matthew Walters, Nicholas J. Wareham, Sylvia Wassertheil-Smoller, James G. Wilson, Kerri L. Wiggins, Qiong Yang, Salim Yusuf, Najaf Amin, Hugo S. Aparicio, Donna K. Arnett, John Attia, Alexa S. Beiser, Claudine Berr, Julie E. Buring, Mariana Bustamante, Valeria Caso, Yu-Ching Cheng, Seung Hoan Choi, Ayesha Chowhan, Natalia Cullell, Jean-François Dartigues, Hossein Delavaran, Pilar Delgado, Marcus Dörr, Gunnar Engström, Ian Ford, Wander S. Gurpreet, Anders Hamsten, Laura Heitsch, Atsushi Hozawa, Laura Ibanez, Andreea Ilinca, Martin Ingelsson, Motoki Iwasaki, Rebecca D. Jackson, Katarina Jood, Pekka Jousilahti, Sara Kaffashian, Lalit Kalra, Masahiro Kamouchi, Takanari Kitazono, Olafur Kjartansson, Manja Kloss, Peter J. Koudstaal, Jerzy Krupinski, Daniel L. Labovitz, Cathy C. Laurie, Christopher R. Levi, Linxin Li, Lars Lind, Cecilia M. Lindgren, Vasileios Lioutas, Yong Mei Liu, Oscar L. Lopez, Hirata Makoto, Nicolas Martinez-Majander, Koichi Matsuda, Naoko Minegishi, Joan Montaner, Andrew P. Morris, Elena Muiño, Martina Müller-Nurasyid, Bo Norrving, Soichi Ogishima, Eugenio A. Parati, Leema Reddy Peddareddygari, Nancy L. Pedersen, Joanna Pera, Markus Perola, Alessandro Pezzini, Silvana Pileggi, Raquel Rabionet, Iolanda Riba-Llena, Marta Ribasés, Jose R. Romero, Jaume Roquer, Anthony G. Rudd, Antti-Pekka Sarin, Ralhan Sarju, Chloe Sarnowski, Makoto Sasaki, Claudia L. Satizabal, Mamoru Satoh, Naveed Sattar, Norie Sawada, Gerli Sibolt, Ásgeir Sigurdsson, Albert Smith, Kenji Sobue, Carolina Soriano-Tárraga, Tara Stanne, O. Colin Stine, David J. Stott, Konstantin Strauch, Takako Takai, Hideo Tanaka, Kozo Tanno, Alexander Teumer, Liisa Tomppo, Nuria P. Torres-Aguila, Emmanuel Touze, Shoichiro Tsugane, Andre G. Uitterlinden, Einar M. Valdimarsson, Sven J. van der Lee, Henry Völzke, Kenji Wakai, David Weir, Stephen R. Williams, Charles D. A. Wolfe, Quenna Wong, Huichun Xu, Taiki Yamaji, Dharambir K. Sanghera, Olle Melander, Christina Jern, Daniel Strbian, Israel Fernandez-Cadenas, W. T. Longstreth, Arndt Rolfs, Jun Hata, Daniel Woo, Jonathan Rosand, Guillaume Pare, Jemma C. Hopewell, Danish Saleheen, Kari Stefansson, Bradford B. Worrall, Steven J. Kittner, Sudha Seshadri, Myriam Fornage, Hugh S. Markus, Joanna M. M. Howson, Yoichiro Kamatani, Stephanie Debette, Martin Dichgans

ABSTRACT

Stroke has multiple etiologies, but the underlying genes and pathways are largely unknown. We conducted a multiancestry genome-wide-association meta-analysis in 521,612 individuals (67,162 cases and 454,450 controls) and discovered 22 new stroke risk loci, bringing the total to 32. We further found shared genetic variation with related vascular traits, including blood pressure, cardiac traits, and venous thromboembolism, at individual loci (n = 18), and using genetic risk scores and linkage-disequilibrium-score regression. Several loci exhibited distinct association and pleiotropy patterns for etiological stroke subtypes. Eleven new susceptibility loci indicate mechanisms not previously implicated in stroke pathophysiology, with prioritization of risk variants and genes accomplished through bioinformatics analyses using extensive functional datasets. Stroke risk loci were significantly enriched in drug targets for antithrombotic therapy. More... »

PAGES

524-537

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  • Journal

    TITLE

    Nature Genetics

    ISSUE

    4

    VOLUME

    50

    Author Affiliations

  • Indian Institute of Science Bangalore
  • University of Bordeaux
  • Centre Hospitalier Universitaire de Bordeaux
  • Osaka University
  • Broad Institute
  • McMaster University
  • Erasmus University Medical Center
  • Kyushu University
  • Lund University
  • Centre Hospitalier Regional et Universitaire de Lille
  • Massachusetts General Hospital
  • University of Washington
  • University of British Columbia
  • University of Lincoln
  • Istituto Neurologico Carlo Besta
  • Mayo Clinic
  • University of Cambridge
  • Hospital Universitari Vall d'Hebron
  • George Washington University
  • Harvard University
  • University of Virginia
  • University of Maryland, Baltimore
  • University of Mississippi Medical Center
  • Washington University in St. Louis
  • University Medical Center Utrecht
  • Boston University
  • Uppsala University
  • University of North Carolina at Chapel Hill
  • Felix Platter-Hospital
  • Johns Hopkins University
  • University of Iceland
  • Fred Hutchinson Cancer Research Center
  • National Institutes of Health
  • Leeds General Infirmary
  • Institute for Molecular Medicine Finland
  • University of Newcastle Australia
  • University of Alabama at Birmingham
  • Wake Forest University
  • Emory University
  • The University of Texas Health Science Center at Houston
  • Autonomous University of Barcelona
  • University of Florida
  • Leiden University Medical Center
  • East Carolina University
  • University of Cincinnati
  • University of Colorado Anschutz Medical Campus
  • Institute of Metabolic Science
  • Universitaire Ziekenhuizen Leuven
  • King's College London
  • Newcastle University
  • Skåne University Hospital
  • University of Gothenburg
  • Karolinska Institute
  • University of Technology Sydney
  • Mayo Clinic
  • Baltimore VA Medical Center
  • National University of Ireland, Galway
  • Kaiser Permanente Washington Health Research Institute
  • University of Edinburgh
  • Brigham and Women's Hospital
  • University of Oxford
  • Harbor–UCLA Medical Center
  • University of Miami
  • University of Tokyo
  • National Institute for Health and Welfare
  • University of Oklahoma Health Sciences Center
  • Medical University of Graz
  • University of Greifswald
  • Jagiellonian University
  • University of Giessen
  • Sahlgrenska University Hospital
  • Austin Health
  • University of Glasgow
  • Albert Einstein College of Medicine
  • McGill University
  • Clinical Gene Networks (Sweden)
  • Icahn School of Medicine at Mount Sinai
  • Institute of Cardiometabolism And Nutrition
  • VA Office of Research and Development
  • Bærum sykehus
  • Imperial College London
  • National Center For Global Health and Medicine
  • Tulane University
  • Ealing Hospital NHS Trust
  • National Heart Lung and Blood Institute
  • University of Helsinki
  • University of Pennsylvania
  • The University of Texas Health Science Center at San Antonio
  • Kyoto University
  • German Center for Neurodegenerative Diseases
  • Boston University School of Medicine
  • University of Kentucky
  • Hunter Medical Research Institute
  • University of Montpellier
  • Center for Research in Environmental Epidemiology
  • University of Perugia
  • German Centre for Cardiovascular Research
  • Dayanand Medical College & Hospital
  • Tohoku Medical Megabank Organization
  • National Cancer Centre
  • The Ohio State University
  • National University Hospital of Iceland
  • University Hospital Heidelberg
  • University Hospital Mútua de Terrassa
  • Montefiore Medical Center
  • John Hunter Hospital
  • Wellcome Centre for Human Genetics
  • Beth Israel Deaconess Medical Center
  • University of Pittsburgh
  • Helsinki University Central Hospital
  • University of Tartu
  • University of Brescia
  • Mario Negri Institute for Pharmacological Research
  • University of Barcelona
  • Hospital Del Mar
  • Iwate Medical University
  • Icelandic Heart Association
  • Ludwig Maximilian University of Munich
  • Nagoya University
  • Université de Caen Basse-Normandie
  • Aichi Cancer Center
  • University of Michigan–Ann Arbor
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41588-018-0058-3

    DOI

    http://dx.doi.org/10.1038/s41588-018-0058-3

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1101510806

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/29531354


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