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Article (Scientific journals)
Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes.
Malik, Rainer; Chauhan, Ganesh; Traylor, Matthew et al.
2018In Nature Genetics, 50 (4), p. 524-537
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Keywords :
Computational Biology; Databases, Genetic; Epigenesis, Genetic; Female; Gene Regulatory Networks; Genetic Loci; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; INDEL Mutation; Linkage Disequilibrium; Male; Models, Genetic; Polymorphism, Single Nucleotide; Risk Factors; Stroke/classification/genetics/physiopathology
Abstract :
[en] 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.
Disciplines :
Genetics & genetic processes
Author, co-author :
Malik, Rainer
Chauhan, Ganesh
Traylor, Matthew
Sargurupremraj, Muralidharan
Okada, Yukinori
Mishra, Aniket
Rutten-Jacobs, Loes
Giese, Anne-Katrin
van der Laan, Sander W.
Gretarsdottir, Solveig
Anderson, Christopher D.
Chong, Michael
Adams, Hieab H. H.
Ago, Tetsuro
Almgren, Peter
Amouyel, Philippe
Ay, Hakan
Bartz, Traci M.
Benavente, Oscar R.
Bevan, Steve
Boncoraglio, Giorgio B.
Brown, Robert D. Jr
Butterworth, Adam S.
Carrera, Caty
Carty, Cara L.
Chasman, Daniel I.
Chen, Wei-Min
Cole, John W.
Correa, Adolfo
Cotlarciuc, Ioana
Cruchaga, Carlos
Danesh, John
de Bakker, Paul I. W.
DeStefano, Anita L.
den Hoed, Marcel
Duan, Qing
Engelter, Stefan T.
Falcone, Guido J.
Gottesman, Rebecca F.
Grewal, Raji P.
Gudnason, Vilmundur
Gustafsson, Stefan
Haessler, Jeffrey
Harris, Tamara B.
Hassan, Ahamad
Havulinna, Aki S.
Heckbert, Susan R.
Holliday, Elizabeth G.
Howard, George
Hsu, Fang-Chi
Hyacinth, Hyacinth I.
Ikram, M. Arfan
Ingelsson, Erik
Irvin, Marguerite R.
Jian, Xueqiu
Jiménez-Conde, Jordi
Johnson, Julie A.
Jukema, J. Wouter
Kanai, Masahiro
Keene, Keith L.
Kissela, Brett M.
Kleindorfer, Dawn O.
Kooperberg, Charles
Kubo, Michiaki
Lange, Leslie A.
Langefeld, Carl D.
Langenberg, Claudia
Launer, Lenore J.
Lee, Jin-Moo
Lemmens, Robin
Leys, Didier
Lewis, Cathryn M.
Lin, Wei-Yu
Lindgren, Arne G.
Lorentzen, Erik
Magnusson, Patrik K.
Maguire, Jane
Manichaikul, Ani
McArdle, Patrick F.
Meschia, James F.
Mitchell, Braxton D.
Mosley, Thomas H.
Nalls, Michael A.
Ninomiya, Toshiharu
O'Donnell, Martin J.
Psaty, Bruce M.
Pulit, Sara L.
Rannikmäe, Kristiina
Reiner, Alexander P.
Rexrode, Kathryn M.
Rice, Kenneth
Rich, Stephen S.
Ridker, Paul M.
Rost, Natalia S.
Rothwell, Peter M.
Rotter, Jerome I.
Rundek, Tatjana
Sacco, Ralph L.
Sakaue, Saori
Sale, Michele M.
Salomaa, Veikko
Sapkota, Bishwa R.
Schmidt, Reinhold
Schmidt, Carsten O.
Schminke, Ulf
Sharma, Pankaj
Slowik, Agnieszka
Sudlow, Cathie L. M.
Tanislav, Christian
Tatlisumak, Turgut
Taylor, Kent D.
Thijs, Vincent N. S.
Thorleifsson, Gudmar
Thorsteinsdottir, Unnur
Tiedt, Steffen
Trompet, Stella
Tzourio, Christophe
van Duijn, Cornelia M.
Walters, Matthew
Wareham, Nicholas J.
Wassertheil-Smoller, Sylvia
Wilson, James G.
Wiggins, Kerri L.
Yang, Qiong
Yusuf, Salim
Bis, Joshua C.
Pastinen, Tomi
Ruusalepp, Arno
Schadt, Eric E.
Koplev, Simon
Björkegren, Johan L. M.
Codoni, Veronica  ;  Institut National de la Santé et de la Recherche Médicale - INSERM > Sorbonne Universités, Université Pierre et Marie Curie, Paris 06, Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche en Santé 1166, F-75013 Paris
Civelek, Mete
Smith, Nicholas L.
Trégouët, David A.
Christophersen, Ingrid E.
Roselli, Carolina
Lubitz, Steven A.
Ellinor, Patrick T.
Tai, E. Shyong
Kooner, Jaspal S.
Kato, Norihiro
He, Jiang
van der Harst, Pim
Elliott, Paul
Chambers, John C.
Takeuchi, Fumihiko
Johnson, Andrew D.
Sanghera, Dharambir K.
Melander, Olle
Jern, Christina
Strbian, Daniel
Fernandez-Cadenas, Israel
Longstreth, W. T. Jr
Rolfs, Arndt
Hata, Jun
Woo, Daniel
Rosand, Jonathan
Pare, Guillaume
Hopewell, Jemma C.
Saleheen, Danish
Stefansson, Kari
Worrall, Bradford B.
Kittner, Steven J.
Seshadri, Sudha
Fornage, Myriam
Markus, Hugh S.
Howson, Joanna M. M.
Kamatani, Yoichiro
Debette, Stephanie
Dichgans, Martin
More authors (161 more) Less
External co-authors :
yes
Language :
English
Title :
Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes.
Publication date :
2018
Journal title :
Nature Genetics
ISSN :
1546-1718
Publisher :
Nature Publishing Group, United Kingdom
Volume :
50
Issue :
4
Pages :
524-537
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBilu :
since 19 December 2022

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