Stroke genetics informs drug discovery and risk prediction across ancestries
Aniket Mishra(Université de Bordeaux), Rainer Malik(LMU Klinikum), Tsuyoshi Hachiya(Iwate Medical University), Tuuli Jürgenson(University of Tartu), Shinichi Namba(The University of Osaka), Daniel Posner(VA Boston Healthcare System), Frederick Kamanu(Brigham and Women's Hospital), Masaru Koido(Tokyo Medical University), Quentin Le Grand(Université de Bordeaux), Mingyang Shi(The University of Tokyo), Yunye He(The University of Tokyo), Marios K. Georgakis(Broad Institute), Ilana Caro(Université de Bordeaux), Kristi Krebs(University of Tartu), Yi‐Ching Liaw(Chung Shan Medical University Hospital), Felix Vaura(University of Turku), Kuang Lin(University of Oxford), Bendik S. Winsvold(Oslo University Hospital), Vinodh Srinivasasainagendra(University of Alabama at Birmingham), Livia Parodi(Broad Institute), Hee‐Joon Bae(Seoul National University Bundang Hospital), Ganesh Chauhan(Rajendra Institute of Medical Sciences), Michael Chong(Thrombosis and Atherosclerosis Research Institute), Liisa Tomppo(University of Helsinki), Rufus Akinyemi(University of Ibadan), Gennady V. Roshchupkin(Erasmus MC), Naomi Habib(Hebrew University of Jerusalem), Yon Ho Jee(Harvard University), Jesper Qvist Thomassen(Copenhagen University Hospital), Vida Abedi(Pennsylvania State University), Jara Cárcel‐Márquez(Universitat Autònoma de Barcelona), Marianne Nygaard(University of Southern Denmark), Hampton L. Leonard(National Institutes of Health), Chaojie Yang(University of Virginia), Ekaterina Yonova-Doing(University of Cambridge), Maria J. Knol(Erasmus MC), Adam Lewis(Vanderbilt University Medical Center), Renae Judy(University of Pennsylvania), Tetsuro Ago(Kyushu University), Philippe Amouyel(Inserm), Nicole D. Armstrong(University of Alabama at Birmingham), Mark K. Bakker(Utrecht University), Traci M. Bartz(University of Washington), David A. Bennett(Rush University Medical Center), Joshua C. Bis(University of Washington), Constance Bordes(Université de Bordeaux), Sigrid Børte(Oslo University Hospital), Anael Cain(Hebrew University of Jerusalem), Paul M. Ridker(Brigham and Women's Hospital), Kelly Cho(VA Boston Healthcare System), Zhengming Chen(University of Oxford), Carlos Cruchaga(Washington University in St. Louis), John W. Cole(University of Maryland, Baltimore), Phil L. de Jager(Broad Institute), Rafael de Cid(Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol), Matthias Endres(German Center for Neurodegenerative Diseases), Leslie Ecker Ferreira(Universidade da Região de Joinville), Mirjam I. Geerlings(Utrecht University), Natalie C. Gasca(University of Washington), Vilmundur Guðnason(University of Iceland), Jun Hata(Kyushu University), Jing He(Vanderbilt University Medical Center), Alicia K. Heath(Imperial College London), Yuk‐Lam Ho(VA Boston Healthcare System), Aki S. Havulinna(Finnish Institute for Health and Welfare), Jemma C. Hopewell(University of Oxford), Hyacinth I. Hyacinth(University of Cincinnati Medical Center), Michael Inouye(Baker Heart and Diabetes Institute), Mina A. Jacob(Radboud University Nijmegen), Christina Jeon(Los Angeles County Department of Public Health), Christina Jern(Sahlgrenska University Hospital), Masahiro Kamouchi(Kyushu University), Keith L. Keene(East Carolina University), Takanari Kitazono(Kyushu University), Steven J. Kittner(University of Maryland, Baltimore), Takahiro Konuma(The University of Osaka), Amit Kumar(Rajendra Institute of Medical Sciences), Paul Lacaze(Monash University), Lenore J. Launer(National Institute on Aging), Keon‐Joo Lee(Korea University Medical Center), Kaido Lepik(SIB Swiss Institute of Bioinformatics), Jiang Li(Geisinger Health System), Liming Li(Peking University), Ani Manichaikul(University of Virginia), Hugh S. Markus(University of Cambridge), Nicholas A. Marston(Brigham and Women's Hospital), Thomas Meitinger(Helmholtz Zentrum München), Braxton D. Mitchell(University of Maryland, Baltimore), Felipe A. Montellano(University of Würzburg), Takayuki Morisaki(Tokyo Medical University), Thomas H. Mosley(Jackson Memorial Hospital), Mike A. Nalls(National Institutes of Health), Børge G. Nordestgaard(University of Copenhagen), Martin O’Donnell(Ollscoil na Gaillimhe – University of Galway), Yukinori Okada(RIKEN Center for Integrative Medical Sciences), N. Charlotte Onland-Moret(Utrecht University), Bruce Ovbiagele(University of California, San Francisco), Annette Peters(Helmholtz Zentrum München), Bruce M. Psaty(University of Washington), Stephen S. Rich(University of Virginia), Jonathan Rosand(Broad Institute), Marc S. Sabatine(Brigham and Women's Hospital), Ralph L. Sacco(University of Miami), Danish Saleheen(Columbia University), Else Charlotte Sandset(Oslo University Hospital), Veikko Salomaa(Finnish Institute for Health and Welfare), Muralidharan Sargurupremraj(The University of Texas at San Antonio Health Science Center), Makoto Sasaki(Iwate Medical University), Claudia L. Satizábal(The University of Texas at San Antonio Health Science Center), Carsten Oliver Schmidt(Universitätsmedizin Greifswald), Atsushi Shimizu(Iwate Medical University), Nicholas Smith(Kaiser Permanente Washington Health Research Institute), Kelly L. Sloane(University of Pennsylvania), Yoichi Sutoh(Iwate Medical University), Yan V. Sun(Emory University), Kozo Tanno(Iwate Medical University), Steffen Tiedt(LMU Klinikum), Turgut Tatlisumak, Nuria P. Torres‐Aguila(Hospital de Sant Pau), Hemant K. Tiwari(University of Alabama at Birmingham), David‐Alexandre Trégouët(Université de Bordeaux), Stella Trompet(Leiden University Medical Center), Anil M Tuladhar(Radboud University Nijmegen), Anne Tybjærg‐Hansen(University of Copenhagen), Marion van Vugt(Utrecht University), Riina Vibo(University of Tartu), Shefali S. Verma(University of Pennsylvania), Kerri L. Wiggins(University of Washington), Patrik Wennberg(Umeå University), Daniel Woo(University of Cincinnati Medical Center), Peter W. F. Wilson(Emory University), Huichun Xu(University of Maryland, Baltimore), Qiong Yang(Boston University), Kyungheon Yoon(Korea National Institute of Health), Joshua C. Bis(University of Washington), Jin‐Moo Lee(Washington University in St. Louis), Yu‐Ching Cheng(University of Maryland, Baltimore), James F. Meschia(Jacksonville College), Wei Min Chen(University of Virginia), Michèle M. Sale(University of Virginia), Alan B. Zonderman(National Institutes of Health), Michele K. Evans(National Institutes of Health), James G. Wilson(Jackson Memorial Hospital), Adolfo Correa(Jackson Memorial Hospital), Matthew Traylor(Oslo University Hospital), Cathryn M. Lewis(Oslo University Hospital), Cara L. Carty(Oslo University Hospital), Alexander Reiner(University of Washington), Jeffrey Haessler(Oslo University Hospital), Carl D. Langefeld(Oslo University Hospital), Rebecca F. Gottesman(Oslo University Hospital), Kristine Yaffe(Oslo University Hospital), Yong Mei Liu(Oslo University Hospital), Charles Kooperberg(Fred Hutch Cancer Center), Leslie A. Lange(University of Colorado Anschutz Medical Campus), Karen L. Furie(Brown University), Donna K. Arnett(University of Kentucky), Oscar R. Benavente(University of British Columbia), Raji P. Grewal(Saint Francis Medical Center), Leema Reddy Peddareddygari(Saint Francis Medical Center), Charles Kooperberg(Fred Hutch Cancer Center), Kristian Hveem(Norwegian University of Science and Technology), Sara Lindstrom(University of Washington), Lu Wang(University of Washington), Erin N. Smith(University of California San Diego), William Gordon(University of Washington), Astrid van Hylckama Vlieg(Leiden University Medical Center), Mariza de Andrade(Mayo Clinic in Florida), Jennifer A. Brody(University of Washington), Jack Pattee(University of Minnesota), Jeffrey Haessler(Oslo University Hospital), Ben M. Brumpton(Norwegian University of Science and Technology), Pierre Suchon(Hôpital de la Timone), Ming‐Huei Chen, Kelly A. Frazer(University of California San Diego), Constance Turman(Harvard University), Marine Germain(Université de Bordeaux), James W. MacDonald(University of Washington), Sigrid K. Brækkan(UiT The Arctic University of Norway), Sebastian M. Armasu(Mayo Clinic in Florida), Nathan Pankratz(University of Minnesota), Rebecca D. Jackson(The Ohio State University), Jonas B. Nielsen(Statens Serum Institut), Franco Giulianini(Brigham and Women's Hospital), Marja K. Puurunen, Manal Ibrahim(Hôpital de la Timone), Susan R. Heckbert(Kaiser Permanente Washington Health Research Institute), Theo K. Bammler(University of Washington), Bryan M. McCauley(Mayo Clinic in Florida), Kent D. Taylor(UCLA Medical Center), James S. Pankow(University of Minnesota), Alex P. Reiner(University of Washington), Maiken E. Gabrielsen(Norwegian University of Science and Technology), Jean-François Deleuze(Commissariat à l'Énergie Atomique et aux Énergies Alternatives), Chris O’Donnell, Jihye Kim(Harvard University), Barbara McKnight(University of Washington), Peter Kraft(Harvard University), John‐Bjarne Hansen(University Hospital of North Norway), Frits R. Rosendaal(Leiden University Medical Center), John A. Heit(Mayo Clinic in Florida), Weihong Tang(University of Minnesota), Pierre‐Emmanuel Morange(Inserm), Andrew D. Johnson, Christopher Kabrhel(Harvard University), The Dutch Parelsnoer Initiative (PSI) Cerebrovascular Disease Study Group(Radboud University Nijmegen), Ewoud J. van Dijk(Erasmus MC), Peter J. Koudstaal(University Medical Center Groningen), Gert-Jan Luijckx(Amsterdam University Medical Centers), Paul J. Nederkoorn(Maastricht University), Robert J van Oostenbrugge(Amsterdam University Medical Centers), Marieke C. Visser(Leiden University Medical Center), Marieke J.H. Wermer(Utrecht University), L. Jaap Kappelle(University of Tartu), The Estonian Biobank(University of Tartu), Tõnu Esko(University of Tartu), Andres Metspalu(University of Tartu), Reedik Mägi(University of Alabama at Birmingham), Mari Nelis(Radboud University Nijmegen), The NINDS Stroke Genetics Network (SiGN)(John Hunter Hospital), Marguerite R. Irvin(University of Technology Sydney), Frank-Erik de Leeuw(Universitat Autònoma de Barcelona), Christopher Levi(Royal Holloway University of London), Jane Maguire(University of Edinburgh), Jordi Jiménez‐Conde(University of Edinburgh), Pankaj Sharma(Medical University of Graz), Cathie Sudlow(Jagiellonian University), Kristiina Rannikmäe(Jagiellonian University), Reinhold Schmidt(The University of Melbourne), Agnieszka Slowik(Lund University), Joanna Pera(Lund University), Vincent Thijs(Lund University), Arne G. Lindgren(Lund University), Andreea Ilinca(Brigham and Women's Hospital), Olle Melander(University of Oxford), Gunnar Engström(University of Gothenburg), Kathryn M. Rexrode(University of Florida), Peter M. Rothwell(University of Cambridge), Tara M. Stanne(University of Cambridge), Julie A. Johnson(Washington University in St. Louis), John Danesh(Fondazione IRCCS Istituto Neurologico Carlo Besta), Adam S. Butterworth(RIKEN Center for Integrative Medical Sciences), Laura Heitsch(University of Brescia), Giorgio B. Boncoraglio(University of Rostock), Michiaki Kubo(Harvard University), Alessandro Pezzini(University of Michigan), Arndt Rolfs(The Ohio State University), Anne‐Katrin Giese(Jacksonville College), David R. Weir(KU Leuven), Rebecca D. Jackson(Lund University), Owen A. Ross(University of Vermont), Robin Lemmons(Sahlgrenska University Hospital), Martin Söderholm(University of Florida), Mary Cushman(University of Cambridge), Katarina Jood(Helmholtz Zentrum München), Caitrin W. McDonough(Chang Gung Memorial Hospital), Steven Bell(University of Helsinki), Birgit Linkohr(Massachusetts General Hospital), Tsong-Hai Lee(University of Pittsburgh), Jukka Putaala(The University of Texas at San Antonio Health Science Center), Christopher D. Anderson(Broad Institute), Oscar L. Lopez(Hospital de Sant Pau), Xueqiu Jian(Universitat Autònoma de Barcelona), Ulf Schminke(Washington University in St. Louis), Natàlia Cullell(Mútua Terrassa), Pilar Delgado, Laura Ibáñez(The University of Tokyo), Jerzy Krupiński(Hospital Universitario Virgen Macarena), Vasileios Lioutas(Hospital de Sant Pau), Koichi Matsuda(Universitat Autònoma de Barcelona), Joan Montaner(The University of Texas Health Science Center at Houston), Elena Muiño(University of Glasgow), Jaume Roquer(University of Helsinki), Chloé Sarnowski(Universitätsmedizin Greifswald), Naveed Sattar(University of Cambridge), Gerli Sibolt(RIKEN Center for Integrative Medical Sciences), Alexander Teumer(Harvard University), Loes C.A. Rutten‐Jacobs(deCODE Genetics (Iceland)), Masahiro Kanai(Harvard University), Anne‐Katrin Giese(Population Health Research Institute), Sólveig Grétarsdóttir(Lund University), Natalia S. Rost, Salim Yusuf(University of Lincoln), Peter Almgren(Mayo Clinic in Arizona), Hakan Ay(Universitat Autònoma de Barcelona), Steve Bevan(Brigham and Women's Hospital), Robert D. Brown(University of Virginia), Caty Carrera(Royal Holloway University of London), Julie E. Buring(Utrecht University), Wei‐Min Chen(Boston University), Ioana Cotlarciuc(Uppsala University), Paul I. W. de Bakker(University of North Carolina at Chapel Hill), Anita L. DeStefano(University of Basel), Marcel den Hoed(Yale University), Qing Duan(Johns Hopkins University), Stefan T. Engelter(Uppsala University), Guido J. Falcone(Leeds General Infirmary), Rebecca F. Gottesman(Oslo University Hospital), Stefan Gustafsson(University of Alabama at Birmingham), Ahamad Hassan(Wake Forest University), Elizabeth G. Holliday(Uppsala University), George Howard(National Institutes of Health), Fang‐Chi Hsu(University of Cincinnati Medical Center), Erik Ingelsson(University of Cincinnati Medical Center), Tamara B. Harris(Queen Mary University of London), Brett Kissela(KU Leuven), Dawn Kleindorfer(Inserm), Claudia Langenberg(University of Cambridge), Robin Lemmens(University of Gothenburg), Didier Leys(Karolinska Institutet), Wei‐Yu Lin(University of Maryland, Baltimore), Erik Lorentzen(Utrecht University), Patrik K. E. Magnusson(University of Washington), Patrick F. McArdle(The University of Osaka), Sara L. Pulit(University of Oklahoma Health Sciences Center), Kenneth Rice(Justus-Liebig-Universität Gießen), Saori Sakaue(deCODE Genetics (Iceland)), Bishwa R. Sapkota(deCODE Genetics (Iceland)), Christian Tanislav, Gudmar Thorleifsson(Erasmus MC), U. Thorsteinsdottir(University of Glasgow), Christophe Tzourio(KU Leuven), Cornelia M. van Duijn(Erasmus MC), James Walters(Boston University), Nicholas J. Wareham(Hunter Medical Research Institute), Najaf Amin(Boston University), Hugo J. Aparicio(Inserm), John Attia(Center for Research in Environmental Epidemiology), Alexa Beiser(University of Perugia), Claudine Berr(Vanderbilt University Medical Center), Mariana Bustamante(Boston University), Valeria Caso, Seung Hoan Choi(Lund University), Ayesha Chowhan(German Centre for Cardiovascular Research), Jean‐François Dartigues(University of Glasgow), Hossein Delavaran(Dayanand Medical College & Hospital), Marcus Dörr(Karolinska Institutet), Ian Ford(Tohoku Medical Megabank Organization), Wander S. Gurpreet(Uppsala University), Anders Hamsten, Atsushi Hozawa(Université de Bordeaux), Martin Ingelsson(King's College London), Motoki Iwasaki(National University Hospital of Iceland), Sara Kaffashian(Heidelberg University), Lalit Kalra(Albert Einstein College of Medicine), Ólafur Kjartansson(University of Washington), Manja Kloß(University of Oxford), Daniel Labovitz(Uppsala University), Cathy C. Laurie(Centre for Human Genetics), Linxin Li(Peking University), Lars Lind(Tohoku Medical Megabank Organization), Cecilia M. Lindgren(Centre for Human Genetics), Makoto Hirata(German Centre for Cardiovascular Research), Naoko Minegishi(Lund University), Andrew P. Morris(The Ohio State University), Martina Müller‐Nurasyid(Fondazione IRCCS Istituto Neurologico Carlo Besta), Bo Norrving(Karolinska Institutet), Soichi Ogishima(Finnish Institute for Health and Welfare), Eugenio Parati(Finnish Institute for Health and Welfare), Nancy L. Pedersen(Mario Negri Institute for Pharmacological Research), Markus Perola(Universitat de Barcelona), Pekka Jousilahti(Universitat Autònoma de Barcelona), Silvana Pileggi(Universitat Autònoma de Barcelona), Raquel Rabionet(Boston University), Iolanda Riba‐Llena(King's College London), Marta Ribasés(The University of Texas at San Antonio Health Science Center), José R. Romero(Dayanand Medical College & Hospital), Anthony G. Rudd(deCODE Genetics (Iceland)), Antti-Pekka Sarin, Sarju Ralhan(deCODE Genetics (Iceland)), Mamoru Satoh(Icelandic Heart Association), Norie Sawada(University of Maryland, Baltimore), Ásgeir Sigurðsson(University of Glasgow), Albert V. Smith(Helmholtz Zentrum München), O. Colin Stine(Tohoku Medical Megabank Organization), David J. Stott(Aichi Cancer Center), Konstantin Strauch(Université de Caen Normandie), Takako Takai, Hideo Tanaka(Erasmus MC), Emmanuel Touzé(Reykjavík University), Shoichiro Tsugane(Erasmus MC), André G. Uitterlinden(Aichi Cancer Center), Einar Már Valdimarsson(Odense University Hospital), Sven J. van der Lee(King's College London), Kenji Wakai(University of Washington), Stephen R. Williams, Charles Wolfe(University of Oklahoma Health Sciences Center), Quenna Wong(deCODE Genetics (Iceland)), Taiki Yamaji(The Lundquist Institute), Dharambir K. Sanghera(University of Helsinki), Kari Stefansson(Iwate Medical University), Kent D. Taylor(Hospital Del Mar), Nicolas Martinez‐Majander(Universitätsmedizin Greifswald), Kenji Sobue(University of Ibadan), Carolina Soriano‐Tárraga(Kwame Nkrumah University of Science and Technology), Henry Völzke(University of Ghana), Onoja Akpa(Ahmadu Bello University), Fred Stephen Sarfo(University of Ilorin Teaching Hospital), Albert Akpalu(Jos University Teaching Hospital), Reginald Obiako(Aminu Kano Teaching Hospital), Kolawole Wahab(Obafemi Awolowo University), Godwin Osaigbovo(Medical University of South Carolina), Lukman Owolabi(University of Ibadan), Morenikeji Komolafe(Ahmadu Bello University), Carolyn Jenkins(University of Ibadan), Oyedunni Arulogun(University of Ibadan), Godwin Ogbole(University of Ibadan), Abiodun M. Adeoye(University of Ibadan), Joshua Akinyemi(University of Ibadan), Atinuke Agunloye(University of Ibadan), Adekunle Fakunle(University of Ibadan), Ezinne Uvere(China National Center for Food Safety Risk Assessment), Abimbola Olalere(University of Oxford), Olayinka Adebajo(University of Oxford), The China Kadoorie Biobank Collaborative Group(Chinese Academy of Medical Sciences & Peking Union Medical College), Junshi Chen(Chinese Academy of Medical Sciences & Peking Union Medical College), Robert Clarke(Peking University), Rory Collins(University of Oxford), Yu Guo(University of Oxford), Chen Wang(University of Oxford), Jun Lv(University of Oxford), Richard Peto(University of Oxford), Yiping Chen(University of Oxford), Zammy Fairhurst-Hunter(University of Oxford), Michael Hill(University of Oxford), Alfred Pozarickij(Peking University), Dan Schmidt(Université de Bordeaux), Becky Stevens(Universidade da Região de Joinville), Iain Turnbull(The University of Tokyo), Canqing Yu(Tokyo Medical University), The VA Million Veteran Program(Utrecht University), Quentin Le Grand(Université de Bordeaux), Leslie Ecker Ferreira(University of Iceland), The Biobank Japan(Utrecht University), Akiko Nagai(National Institute of Neurological Disorders and Stroke), Yoishinori Murakami(National Institutes of Health), Mirjam I. Geerlings(Utrecht University), Natalie C. Gasca(University of Washington), Vilmundur Guðnason(University of Iceland), Marion van Vugt(The University of Texas at San Antonio Health Science Center), Rebecca F. Gottesman(Boston University), Eric J. Shiroma(Erasmus MC), Sigurður Sigurðsson(German Centre for Cardiovascular Research), Mohsen Ghanbari(Columbia University Irving Medical Center), Eric Boerwinkle(Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol), Alexa Beiser(University of Copenhagen), Bernard Fongang(The University of Texas at San Antonio Health Science Center), Ruiqi Wang(University of Pennsylvania), M. Kamran Ikram(Erasmus MC), Uwe Völker(Amphia Ziekenhuis), Phil L. de Jager(Broad Institute), Rafael de Cid(Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol), Børge G. Nordestgaard(University of Copenhagen), Muralidharan Sargurupremraj(Radboud University Nijmegen), Shefali S. Verma(Amsterdam University Medical Centers), The ODYSSEY Study(Sint Franciscus Gasthuis), Karlijn F. de Laat(Canisius-Wilhelmina Ziekenhuis), Anouk G.W. van Norden(Medisch Centrum Leeuwarden), Paul L.M. de Kort(Norwegian University of Science and Technology), Sarah E. Vermeer(Norwegian University of Science and Technology), Paul J.A.M. Brouwers(University of Bristol), Rob A.R. Gons(University of Michigan), Paul J. Nederkoorn(Oslo University Hospital), Tom den Heijer(Norwegian University of Science and Technology), Gert W. van Dijk(University of Michigan), Frank G. W. van Rooij(Oslo University Hospital), HUNT All-In Stroke(Norwegian University of Science and Technology), Anne Hege Aamodt(Norwegian University of Science and Technology), Anne Heidi Skogholt(University of Michigan), Ben M. Brumpton(University of Oslo), Cristen J. Willer(University of Oslo), Ingrid Heuch(Statens Serum Institut), Knut Hagen(Norwegian University of Science and Technology), Lars G. Fritsche(Norwegian University of Science and Technology), Linda M. Pedersen(University of Duisburg-Essen), Maiken E. Gabrielsen(Universitätsklinikum Würzburg), Hanne Ellekjær(University of Würzburg), Wei Zhou(Hospital de Sant Pau), Amy E. Martinsen(Institut d'Investigacions Biomèdiques de Barcelona), Espen Saxhaug Kristoffersen(Hospital de Sant Pau), Jonas B. Nielsen(Instituto de Investigación Sanitaria de Santiago), Kristian Hveem(Instituto de Investigación Sanitaria de Santiago), Laurent F. Thomas(Instituto de Investigación Sanitaria de Santiago), The SICFAIL Study(BioCruces Health research Institute), Christoph Kleinschnitz(Universidad de Valladolid), Stefan Frantz(Hospital Clínic de Barcelona), Kathrin Ungethüm(Vall d'Hebron Hospital Universitari), The Generacion Study(Vall d'Hebron Hospital Universitari), Cristina Gallego-Fábrega(Vall d'Hebron Hospital Universitari), Miquel Lledós(Universitat Autònoma de Barcelona), Laia Llucià‐Carol(Hospital Universitario Central de Asturias), Tomás Sobrino(Universitat Autònoma de Barcelona), Francisco Campos(Health Research Institute of the Balearic Islands), José Castillo(Health Research Institute of the Balearic Islands), Marimar Freijó(Hospital General Universitario de Albacete), Juan F. Arenillas(Hospital General Universitario de Albacete), Vı́ctor Obach(Universitat Autònoma de Barcelona), José Álvarez‐Sabín(Washington University in St. Louis), Carlos A. Molina(Hospital de Sant Pau), Marc Ribó(Hospital de Sant Pau), Lucía Muñoz-Narbona(Hospital de Sant Pau), Elena López‐Cancio(Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol), Mónica Millán(Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol), Rosa Díaz-Navarro(Hospital de Sant Pau), Cristòfol Vives-Bauzá(Frederiksberg Hospital), Gemma Serrano‐Heras(Frederiksberg Hospital), Tomás Segura(University of Copenhagen), Pilar Delgado(University of Copenhagen), Rajat Dhar(Gentofte Hospital), Raquel Delgado‐Mederos(Utrecht University), Luis Prats-Sánchez(Utrecht University), Pol Camps‐Renom(Columbia University), Natàlia Blay(Helmholtz Zentrum München), Lauro Sumoy(University of Helsinki), Joan Martí‐Fábregas(University of Helsinki), The Copenhagen City Heart Study(University of Helsinki), Peter Schnohr(Columbia University Irving Medical Center), Gorm Boje Jensen(Washington University in St. Louis), Marianne Benn(Washington University in St. Louis), Shoaib Afzal, Pia R. Kamstrup(McGill University), The SMART Study(Utrecht University), Jessica van Setten(Imperial College London), Sander W. van der Laan(University of Oxford), Jet M. J. Vonk(Helmholtz Zentrum München), Bong‐Jo Kim(Kyushu University), Helsinki Stroke Project(Universitätsmedizin Greifswald), Sami Curtze(Netherlands Heart Institute), Marjaana Tiainen(Utrecht University), Janne Kinnunen(University of Helsinki), Follow-up Studies(Korea National Institute of Health), Vilas Menon(Chung Shan Medical University), Yun Ju Sung(Broad Institute), Chengran Yang(University of Cambridge), Florence Saillour-Glenisson(University of Alabama at Birmingham), Simon Gravel(Adolfo Ibáñez University), EPIC-CVD(Albert Einstein College of Medicine), N. Charlotte Onland-Moret(University of Southern Denmark), Alicia K. Heath(Erasmus MC), Iona Y. Millwood(University of Miami), Christian Gieger(Helmholtz Zentrum München), Toshiharu Ninomiya(Kyushu University), Hans J. Grabe(Universitätsmedizin Greifswald), J. Wouter Jukema(Leiden University Medical Center), Ina L. Rissanen(Utrecht University), Daniel Strbian(University of Helsinki), Young Jin Kim(Pennsylvania State University), Pei-Hsin Chen(Rajendra Institute of Medical Sciences), Ernst Mayerhofer(Broad Institute), Joanna M. M. Howson(Radboud University Nijmegen), Marguerite R. Irvin(Carl von Ossietzky Universität Oldenburg), Hieab H.H. Adams(Adolfo Ibáñez University), Sylvia Wassertheil‐Smoller(Albert Einstein College of Medicine), Kaare Christensen(University of Southern Denmark), M. Arfan Ikram(University of Washington), Tatjana Rundek(University of Miami), Bradford B. Worrall(University of Virginia), G.M. Lathrop(Population Health Research Institute), Moeen Riaz(Philadelphia VA Medical Center), Eleanor M. Simonsick(Brigham and Women's Hospital), Janika Kõrv(UCLA Medical Center), Paulo Henrique Condeixa de França(Brigham and Women's Hospital), Ramin Zand(Oslo University Hospital), Kameshwar Prasad(Turku University Hospital), Ruth Frikke‐Schmidt(University of Copenhagen), Frank-Erik de Leeuw(Radboud University Nijmegen), Thomas Liman(Boston University), Karl Georg Hæusler(Hospital de Sant Pau), Ynte M. Ruigrok(Utrecht University), Peter U. Heuschmann(Brigham and Women's Hospital), W. T. Longstreth(University of Ibadan), Keum Ji Jung(Yonsei University), Lisa Bastarache(University of Tartu), Guillaume Paré(Population Health Research Institute), Scott M. Damrauer(German Center for Neurodegenerative Diseases), Daniel I. Chasman(Brigham and Women's Hospital), Jerome I. Rotter(UCLA Medical Center), Christopher D. Anderson(Broad Institute), John‐Anker Zwart(Oslo University Hospital), Teemu Niiranen(University of Turku), Myriam Fornage(Brown Foundation), Yung‐Po Liaw(Chung Shan Medical University Hospital), Sudha Seshadri(Boston University), Israel Fernández‐Cadenas(Hospital de Sant Pau), Robin Walters(University of Oxford), Christian T. Ruff(Brigham and Women's Hospital), Mayowa Owolabi(University of Ibadan), Jennifer E. Huffman(VA Boston Healthcare System), Lili Milani(University of Tartu), Yoichiro Kamatani(The University of Tokyo), Martin Dichgans(German Center for Neurodegenerative Diseases), Stéphanie Debette(Université de Bordeaux)
Cited by 591Open Access
Abstract
Abstract Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry 1,2 . Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated ( P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis 3 , and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN ) and variants (such as at GRK5 and NOS3 ). Using a three-pronged approach 4 , we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry 5 . Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.
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