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

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 BevanGiorgio 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 Jimenez-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 Rannikmae, 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. Bjorkegren, Veronica Codoni, Mete Civelek, Nicholas L. Smith, David A. Tregouet, 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, 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-Francois Dartigues, Hossein Delavaran, Pilar Delgado, Marcus Dorr, Gunnar Engstrom, 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, et al.

Research output: Contribution to journalArticlepeer-review

1094 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)524-537
Number of pages14
JournalNature Genetics
Volume50
Issue number4
DOIs
Publication statusPublished - 2018

Fingerprint

Dive into the research topics of 'Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes'. Together they form a unique fingerprint.

Cite this