Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes
Malik, Rainer , Chauhan, Ganesh Traylor, Matthew Sargurupremraj, Muralidharan Okada, Yukinori Mishra, Aniket Rutten-Jacobs, Loes Giese, Anne-Katrin van der Laan, Sander W.
Malik, Rainer
,
Chauhan, Ganesh
Traylor, Matthew
Sargurupremraj, Muralidharan
Okada, Yukinori
Mishra, Aniket
Rutten-Jacobs, Loes
Giese, Anne-Katrin
van der Laan, Sander W.
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Publication Date
2018-03-12
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Article
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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.; 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; 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.; 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; 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.; 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.; Hoed, Marcel den; 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; Amin, Najaf; Aparicio, Hugo S.; Arnett, Donna K.; Attia, John; Beiser, Alexa S.; Berr, Claudine; Buring, Julie E.; Bustamante, Mariana; Caso, Valeria; Cheng, Yu-Ching; Choi, Seung Hoan; Chowhan, Ayesha; Cullell, Natalia; Dartigues, Jean-François; Delavaran, Hossein; Delgado, Pilar; Dörr, Marcus; Engström, Gunnar; Ford, Ian; Gurpreet, Wander S.; Hamsten, Anders; Heitsch, Laura; Hozawa, Atsushi; Ibanez, Laura; Ilinca, Andreea; Ingelsson, Martin; Iwasaki, Motoki; Jackson, Rebecca D.; Jood, Katarina; Jousilahti, Pekka; Kaffashian, Sara; Kalra, Lalit; Kamouchi, Masahiro; Kitazono, Takanari; Kjartansson, Olafur; Kloss, Manja; Koudstaal, Peter J.; Krupinski, Jerzy; Labovitz, Daniel L.; Laurie, Cathy C.; Levi, Christopher R.; Li, Linxin; Lind, Lars; Lindgren, Cecilia M.; Lioutas, Vasileios; Liu, Yong Mei; Lopez, Oscar L.; Makoto, Hirata; Martinez-Majander, Nicolas; Matsuda, Koichi; Minegishi, Naoko; Montaner, Joan; Morris, Andrew P.; Muiño, Elena; Müller-Nurasyid, Martina; Norrving, Bo; Ogishima, Soichi; Parati, Eugenio A.; Peddareddygari, Leema Reddy; Pedersen, Nancy L.; Pera, Joanna; Perola, Markus; Pezzini, Alessandro; Pileggi, Silvana; Rabionet, Raquel; Riba-Llena, Iolanda; Ribasés, Marta; Romero, Jose R.; Roquer, Jaume; Rudd, Anthony G.; Sarin, Antti-Pekka; Sarju, Ralhan; Sarnowski, Chloe; Sasaki, Makoto; Satizabal, Claudia L.; Satoh, Mamoru; Sattar, Naveed; Sawada, Norie; Sibolt, Gerli; Sigurdsson, Ásgeir; Smith, Albert; Sobue, Kenji; Soriano-Tárraga, Carolina; Stanne, Tara; Stine, O. Colin; Stott, David J.; Strauch, Konstantin; Takai, Takako; Tanaka, Hideo; Tanno, Kozo; Teumer, Alexander; Tomppo, Liisa; Torres-Aguila, Nuria P.; Touze, Emmanuel; Tsugane, Shoichiro; Uitterlinden, Andre G.; Valdimarsson, Einar M.; van der Lee, Sven J.; Völzke, Henry; Wakai, Kenji; Weir, David; Williams, Stephen R.; Wolfe, Charles D. A.; Wong, Quenna; Xu, Huichun; Yamaji, Taiki; Sanghera, Dharambir K.; Melander, Olle; Jern, Christina; Strbian, Daniel; Fernandez-Cadenas, Israel; Longstreth, W. T.; 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; , ; , ; , ; , ; , ; , ; , ; , ; , ; , ; , ; , ; , ; , ; , (2018). Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes. Nature Genetics 50 (4),
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 sub-types. 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.
Funder
Publisher
Springer Nature
Publisher DOI
10.1038/s41588-018-0058-3
Rights
Attribution-NonCommercial-NoDerivs 3.0 Ireland