Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes.
| Citation | . “Multiancestry Genome-Wide Association Study Of 520,000 Subjects Identifies 32 Loci Associated With Stroke And Stroke Subtypes.”. Nature Genetics, pp. 524-537. |
| Center | UCSD-UCLA |
| Author | 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, Arfan Ikram, Erik Ingelsson, Marguerite R Irvin, Xueqiu Jian, Jordi Jiménez-Conde, Julie A Johnson, 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, AFGen Consortium, Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium, International Genomics of Blood Pressure Consortium, INVENT Consortium, STARNET, 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, Shyong Tai, Jaspal S Kooner, Norihiro Kato, Jiang He, Pim van der Harst, Paul Elliott, John C Chambers, Fumihiko Takeuchi, Andrew D Johnson, BioBank Japan Cooperative Hospital Group, COMPASS Consortium, EPIC-CVD Consortium, EPIC-InterAct Consortium, International Stroke Genetics Consortium, METASTROKE Consortium, Neurology Working Group of the CHARGE Consortium, NINDS Stroke Genetics Network, UK Young Lacunar DNA Study, MEGASTROKE Consortium, Dharambir K Sanghera, Olle Melander, Christina Jern, Daniel Strbian, Israel Fernandez-Cadenas, W T Longstreth, Arndt Rolfs, Jun Hata, Daniel Woo, Jonathan Rosand, Guillaume Paré, 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, Stéphanie 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. |
| Year of Publication |
2018
|
| Journal |
Nature genetics
|
| Volume |
50
|
| Issue |
4
|
| Number of Pages |
524-537
|
| Date Published |
12/2018
|
| ISSN Number |
1546-1718
|
| DOI |
10.1038/s41588-018-0058-3
|
| Alternate Journal |
Nat. Genet.
|
| PMID |
29531354
|
| PMCID |
PMC5968830
|
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