| Literature DB >> 29531354 |
Rainer Malik1, Ganesh Chauhan2, Matthew Traylor3, Muralidharan Sargurupremraj4,5, Yukinori Okada6,7,8, Kari Stefansson9,10, Bradford B Worrall11, Steven J Kittner12, Sudha Seshadri13,14, Myriam Fornage15,16, Hugh S Markus3, Joanna M M Howson17, Yoichiro Kamatani6,18, Stephanie Debette19,20, Martin Dichgans21,22,23, Aniket Mishra4,5, Loes Rutten-Jacobs3, Anne-Katrin Giese24, Sander W van der Laan25, Solveig Gretarsdottir9, Christopher D Anderson26,27,28, Michael Chong29, Hieab H H Adams30,31, Tetsuro Ago32, Peter Almgren33, Philippe Amouyel34,35, Hakan Ay27,36, Traci M Bartz37, Oscar R Benavente38, Steve Bevan39, Giorgio B Boncoraglio40, Robert D Brown41, Adam S Butterworth17,42, Caty Carrera43,44, Cara L Carty45,46, Daniel I Chasman47,48, Wei-Min Chen49, John W Cole12, Adolfo Correa50, Ioana Cotlarciuc51, Carlos Cruchaga52,53, John Danesh17,54,55,56, Paul I W de Bakker57,58, Anita L DeStefano59,13, Marcel den Hoed60, Qing Duan61, Stefan T Engelter62,63, Guido J Falcone64,65, Rebecca F Gottesman66, Raji P Grewal67, Vilmundur Gudnason68,10, Stefan Gustafsson69, Jeffrey Haessler70, Tamara B Harris71, Ahamad Hassan72, Aki S Havulinna73,74, Susan R Heckbert75, Elizabeth G Holliday76,77, George Howard78, Fang-Chi Hsu79, Hyacinth I Hyacinth80, M Arfan Ikram30, Erik Ingelsson81,69, Marguerite R Irvin82, Xueqiu Jian15, Jordi Jiménez-Conde83, Julie A Johnson84,85, J Wouter Jukema86, Masahiro Kanai6,7,87, Keith L Keene88,89, Brett M Kissela90, Dawn O Kleindorfer90, Charles Kooperberg70, Michiaki Kubo91, Leslie A Lange92, Carl D Langefeld93, Claudia Langenberg94, Lenore J Launer95, Jin-Moo Lee96, Robin Lemmens97,98, Didier Leys99, Cathryn M Lewis100,101, Wei-Yu Lin17,102, Arne G Lindgren103,104, Erik Lorentzen105, Patrik K Magnusson106, Jane Maguire107, Ani Manichaikul49, Patrick F McArdle108, James F Meschia109, Braxton D Mitchell108,110, Thomas H Mosley111,112, Michael A Nalls113,114, Toshiharu Ninomiya115, Martin J O'Donnell29,116, Bruce M Psaty117,75,118,119, Sara L Pulit57,120, Kristiina Rannikmäe121,122, Alexander P Reiner75,123, Kathryn M Rexrode124, Kenneth Rice125, Stephen S Rich49, Paul M Ridker47,48, Natalia S Rost24,27, Peter M Rothwell126, Jerome I Rotter127,128, Tatjana Rundek129, Ralph L Sacco129, Saori Sakaue7,130, Michele M Sale131, Veikko Salomaa73, Bishwa R Sapkota132, Reinhold Schmidt133, Carsten O Schmidt134, Ulf Schminke135, Pankaj Sharma51, Agnieszka Slowik136, Cathie L M Sudlow121,122, Christian Tanislav137, Turgut Tatlisumak138,139, Kent D Taylor127,128, Vincent N S Thijs140,141, Gudmar Thorleifsson9, Unnur Thorsteinsdottir9, Steffen Tiedt1, Stella Trompet142, Christophe Tzourio5,143,144, Cornelia M van Duijn145,146, Matthew Walters147, Nicholas J Wareham94, Sylvia Wassertheil-Smoller148, James G Wilson149, Kerri L Wiggins117, Qiong Yang59, Salim Yusuf29, Joshua C Bis117, Tomi Pastinen150, Arno Ruusalepp151,152,153, Eric E Schadt154, Simon Koplev154, Johan L M Björkegren154,155,156,153, Veronica Codoni157,158, Mete Civelek131,159, Nicholas L Smith75,160,161, David A Trégouët157,158, Ingrid E Christophersen65,162,163, Carolina Roselli65, Steven A Lubitz65,162, Patrick T Ellinor65,162, E Shyong Tai164, Jaspal S Kooner165, Norihiro Kato166, Jiang He167, Pim van der Harst168, Paul Elliott169, John C Chambers170,171, Fumihiko Takeuchi166, Andrew D Johnson13,172, Dharambir K Sanghera132,173,174, Olle Melander33, Christina Jern175, Daniel Strbian176,177, Israel Fernandez-Cadenas43,44, W T Longstreth75,178, Arndt Rolfs179, Jun Hata115, Daniel Woo90, Jonathan Rosand26,27,28, Guillaume Pare29, Jemma C Hopewell180, Danish Saleheen181.
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.Entities:
Mesh：
Year: 2018 PMID： 29531354 PMCID： PMC5968830 DOI： 10.1038/s41588-018-0058-3
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330