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

So rather than solve ANY of the problems in stroke, lets be lazy and just identify more risk factors. God, do we need some stroke leadership that puts a strategy out there for 100% recovery and follows through. Only 425 scientists than need reaming out by the president of that great stroke association to actually solve the correct problems in stroke.
https://www.nature.com/articles/s41588-018-0058-3

• Rainer Malik^1 na3,
• Ganesh Chauhan^2 na3,
• Matthew Traylor  ORCID: orcid.org/0000-0001-6624-8621^3 na3,
• Muralidharan Sargurupremraj^4,5 na3,
• Yukinori Okada  ORCID: orcid.org/0000-0002-0311-8472^6,7,8 na3,
• Aniket Mishra^4,5,
• Loes Rutten-Jacobs  ORCID: orcid.org/0000-0003-3223-885X³,
• Anne-Katrin Giese⁹,
• Sander W. van der Laan  ORCID: orcid.org/0000-0001-6888-1404¹⁰,
• Solveig Gretarsdottir¹¹,
• Christopher D. Anderson^12,13,14,
• Michael Chong¹⁵,
• Hieab H. H. Adams  ORCID: orcid.org/0000-0003-3687-2508^16,17,
• Tetsuro Ago¹⁸,
• Peter Almgren  ORCID: orcid.org/0000-0002-0473-0241¹⁹,
• Philippe Amouyel  ORCID: orcid.org/0000-0001-9088-234X^20,21,
• Hakan Ay^13,22,
• Traci M. Bartz²³,
• Oscar R. Benavente²⁴,
• Steve Bevan²⁵,
• Giorgio B. Boncoraglio²⁶,
• Robert D. Brown Jr²⁷,
• Adam S. Butterworth^28,29,
• Caty Carrera^30,31,
• Cara L. Carty^32,33,
• Daniel I. Chasman^34,35,
• Wei-Min Chen³⁶,
• John W. Cole³⁷,
• Adolfo Correa  ORCID: orcid.org/0000-0002-9501-600X³⁸,
• Ioana Cotlarciuc³⁹,
• Carlos Cruchaga  ORCID: orcid.org/0000-0002-0276-2899^40,41,
• John Danesh^28,42,43,44,
• Paul I. W. de Bakker^45,46,
• Anita L. DeStefano^47,48,
• Marcel den Hoed  ORCID: orcid.org/0000-0001-8081-428X⁴⁹,
• Qing Duan⁵⁰,
• Stefan T. Engelter^51,52,
• Guido J. Falcone^53,54,
• Rebecca F. Gottesman⁵⁵,
• Raji P. Grewal⁵⁶,
• Vilmundur Gudnason^57,58,
• Stefan Gustafsson  ORCID: orcid.org/0000-0001-5894-0351⁵⁹,
• Jeffrey Haessler⁶⁰,
• Tamara B. Harris⁶¹,
• Ahamad Hassan⁶²,
• Aki S. Havulinna  ORCID: orcid.org/0000-0002-4787-8959^63,64,
• Susan R. Heckbert⁶⁵,
• Elizabeth G. Holliday^66,67,
• George Howard⁶⁸,
• Fang-Chi Hsu⁶⁹,
• Hyacinth I. Hyacinth⁷⁰,
• M. Arfan Ikram  ORCID: orcid.org/0000-0003-0372-8585¹⁶,
• Erik Ingelsson^71,72,
• Marguerite R. Irvin⁷³,
• Xueqiu Jian⁷⁴,
• Jordi Jiménez-Conde⁷⁵,
• Julie A. Johnson^76,77,
• J. Wouter Jukema  ORCID: orcid.org/0000-0002-3246-8359⁷⁸,
• Masahiro Kanai  ORCID: orcid.org/0000-0001-5165-4408^6,7,79,
• Keith L. Keene^80,81,
• Brett M. Kissela⁸²,
• Dawn O. Kleindorfer⁸²,
• Charles Kooperberg⁶⁰,
• Michiaki Kubo⁸³,
• Leslie A. Lange⁸⁴,
• Carl D. Langefeld⁸⁵,
• Claudia Langenberg⁸⁶,
• Lenore J. Launer⁸⁷,
• Jin-Moo Lee⁸⁸,
• Robin Lemmens^89,90,
• Didier Leys⁹¹,
• Cathryn M. Lewis  ORCID: orcid.org/0000-0002-8249-8476^92,93,
• Wei-Yu Lin  ORCID: orcid.org/0000-0002-9267-7988^28,94,
• Arne G. Lindgren^95,96,
• Erik Lorentzen⁹⁷,
• Patrik K. Magnusson  ORCID: orcid.org/0000-0002-7315-7899⁹⁸,
• Jane Maguire⁹⁹,
• Ani Manichaikul³⁶,
• Patrick F. McArdle¹⁰⁰,
• James F. Meschia¹⁰¹,
• Braxton D. Mitchell^100,102,
• Thomas H. Mosley^103,104,
• Michael A. Nalls^105,106,
• Toshiharu Ninomiya¹⁰⁷,
• Martin J. O’Donnell^15,108,
• Bruce M. Psaty^{109,110,111,112},
• Sara L. Pulit  ORCID: orcid.org/0000-0002-2502-3669^45,113,
• Kristiina Rannikmäe^114,115,
• Alexander P. Reiner^65,116,
• Kathryn M. Rexrode¹¹⁷,
• Kenneth Rice¹¹⁸,
• Stephen S. Rich³⁶,
• Paul M. Ridker^34,35,
• Natalia S. Rost^9,13,
• Peter M. Rothwell¹¹⁹,
• Jerome I. Rotter^120,121,
• Tatjana Rundek¹²²,
• Ralph L. Sacco¹²²,
• Saori Sakaue^7,123,
• Michele M. Sale¹²⁴,
• Veikko Salomaa⁶³,
• Bishwa R. Sapkota¹²⁵,
• Reinhold Schmidt¹²⁶,
• Carsten O. Schmidt¹²⁷,
• Ulf Schminke¹²⁸,
• Pankaj Sharma³⁹,
• Agnieszka Slowik¹²⁹,
• Cathie L. M. Sudlow^114,115,
• Christian Tanislav¹³⁰,
• Turgut Tatlisumak^131,132,
• Kent D. Taylor^120,121,
• Vincent N. S. Thijs^133,134,
• Gudmar Thorleifsson¹¹,
• Unnur Thorsteinsdottir¹¹,
• Steffen Tiedt¹,
• Stella Trompet¹³⁵,
• Christophe Tzourio^5,136,137,
• Cornelia M. van Duijn^138,139,
• Matthew Walters¹⁴⁰,
• Nicholas J. Wareham⁸⁶,
• Sylvia Wassertheil-Smoller¹⁴¹,
• James G. Wilson¹⁴²,
• Kerri L. Wiggins  ORCID: orcid.org/0000-0003-2749-1279¹⁰⁹,
• Qiong Yang  ORCID: orcid.org/0000-0002-3658-1375⁴⁷,
• Salim Yusuf¹⁵,
• Joshua C. Bis¹⁰⁹,
• Tomi Pastinen¹⁴³,
• Arno Ruusalepp^144,145,146,
• Eric E. Schadt  ORCID: orcid.org/0000-0002-7892-8808¹⁴⁷,
• Simon Koplev  ORCID: orcid.org/0000-0002-8586-5614¹⁴⁷,
• Johan L. M. Björkegren^{147,148,149,150},
• Veronica Codoni^151,152,
• Mete Civelek  ORCID: orcid.org/0000-0002-8141-0284^124,153,
• Nicholas L. Smith^65,154,155,
• David A. Trégouët  ORCID: orcid.org/0000-0001-9084-7800^151,152,
• Ingrid E. Christophersen  ORCID: orcid.org/0000-0002-6141-4712^54,156,157,
• Carolina Roselli  ORCID: orcid.org/0000-0001-5267-6756⁵⁴,
• Steven A. Lubitz^54,156,
• Patrick T. Ellinor  ORCID: orcid.org/0000-0002-2067-0533^54,156,
• E. Shyong Tai¹⁵⁸,
• Jaspal S. Kooner¹⁵⁹,
• Norihiro Kato¹⁶⁰,
• Jiang He¹⁶¹,
• Pim van der Harst  ORCID: orcid.org/0000-0002-2713-686X¹⁶²,
• Paul Elliott  ORCID: orcid.org/0000-0002-7511-5684¹⁶³,
• John C. Chambers^164,165,
• Fumihiko Takeuchi  ORCID: orcid.org/0000-0003-3185-5661¹⁶⁰,
• Andrew D. Johnson^48,166,
• Dharambir K. Sanghera^125,167,168,
• Olle Melander¹⁹,
• Christina Jern  ORCID: orcid.org/0000-0002-7531-2354¹⁶⁹,
• Daniel Strbian^170,171,
• Israel Fernandez-Cadenas^30,31,
• W. T. Longstreth Jr^65,172,
• Arndt Rolfs¹⁷³,
• Jun Hata¹⁰⁷,
• Daniel Woo⁸²,
• Jonathan Rosand^12,13,14,
• Guillaume Pare¹⁵,
• Jemma C. Hopewell¹⁷⁴,
• Danish Saleheen  ORCID: orcid.org/0000-0001-6193-020X¹⁷⁵,
• Kari Stefansson^11,176 na4,
• Bradford B. Worrall^177 na4,
• Steven J. Kittner^37 na4,
• Sudha Seshadri^48,178 na4,
• Myriam Fornage^74,179 na4,
• Hugh S. Markus^3 na4,
• Joanna M. M. Howson^28 na4,
• Yoichiro Kamatani  ORCID: orcid.org/0000-0001-8748-5597^6,180 na4,
• Stephanie Debette^4,5 na4,
• Martin Dichgans  ORCID: orcid.org/0000-0002-0654-387X^{1,181,182 na4},
• Rainer Malik¹,
• Ganesh Chauhan²,
• Matthew Traylor³,
• Muralidharan Sargurupremraj^4,5,
• Yukinori Okada^6,7,8,
• Aniket Mishra^4,5,
• Loes Rutten-Jacobs³,
• Anne-Katrin Giese⁹,
• Sander W. van der Laan¹⁰,
• Solveig Gretarsdottir¹¹,
• Christopher D. Anderson^12,13,14,
• Michael Chong¹⁵,
• Hieab H. H. Adams  ORCID: orcid.org/0000-0003-3687-2508^16,17,
• Tetsuro Ago¹⁸,
• Peter Almgren¹⁹,
• Philippe Amouyel^20,21,
• Hakan Ay^13,22,
• Traci M. Bartz²³,
• Oscar R. Benavente²⁴,
• Steve Bevan²⁵,
• Giorgio B. Boncoraglio²⁶,
• Robert D. Brown Jr²⁷,
• Adam S. Butterworth^28,29,
• Caty Carrera^30,31,
• Cara L. Carty^32,33,
• Daniel I. Chasman^34,35,
• Wei-Min Chen³⁶,
• John W. Cole³⁷,
• Adolfo Correa³⁸,
• Ioana Cotlarciuc³⁹,
• Carlos Cruchaga^40,41,
• John Danesh^28,42,43,44,
• Paul I. W. de Bakker^45,46,
• Anita L. DeStefano^47,48,
• Marcel den Hoed⁴⁹,
• Qing Duan⁵⁰,
• Stefan T. Engelter^51,52,
• Guido J. Falcone^53,54,
• Rebecca F. Gottesman⁵⁵,
• Raji P. Grewal⁵⁶,
• Vilmundur Gudnason^57,58,
• Stefan Gustafsson⁵⁹,
• Jeffrey Haessler⁶⁰,
• Tamara B. Harris⁶¹,
• Ahamad Hassan⁶²,
• Aki S. Havulinna^63,64,
• Susan R. Heckbert⁶⁵,
• Elizabeth G. Holliday^66,67,
• George Howard⁶⁸,
• Fang-Chi Hsu⁶⁹,
• Hyacinth I. Hyacinth⁷⁰,
• M. Arfan Ikram  ORCID: orcid.org/0000-0003-0372-8585¹⁶,
• Erik Ingelsson^71,72,
• Marguerite R. Irvin⁷³,
• Xueqiu Jian⁷⁴,
• Jordi Jiménez-Conde⁷⁵,
• Julie A. Johnson^76,77,
• J. Wouter Jukema⁷⁸,
• Masahiro Kanai^6,7,79,
• Keith L. Keene^80,81,
• Brett M. Kissela⁸²,
• Dawn O. Kleindorfer⁸²,
• Charles Kooperberg⁶⁰,
• Michiaki Kubo⁸³,
• Leslie A. Lange⁸⁴,
• Carl D. Langefeld⁸⁵,
• Claudia Langenberg⁸⁶,
• Lenore J. Launer⁸⁷,
• Jin-Moo Lee⁸⁸,
• Robin Lemmens^89,90,
• Didier Leys⁹¹,
• Cathryn M. Lewis^92,93,
• Wei-Yu Lin^28,94,
• Arne G. Lindgren^95,96,
• Erik Lorentzen⁹⁷,
• Patrik K. Magnusson  ORCID: orcid.org/0000-0002-7315-7899⁹⁸,
• Jane Maguire⁹⁹,
• Ani Manichaikul³⁶,
• Patrick F. McArdle¹⁰⁰,
• James F. Meschia¹⁰¹,
• Braxton D. Mitchell^100,102,
• Thomas H. Mosley^103,104,
• Michael A. Nalls^105,106,
• Toshiharu Ninomiya¹⁰⁷,
• Martin J. O’Donnell^15,108,
• Bruce M. Psaty^{109,110,111,112},
• Sara L. Pulit  ORCID: orcid.org/0000-0002-2502-3669^45,113,
• Kristiina Rannikmäe^114,115,
• Alexander P. Reiner^65,116,
• Kathryn M. Rexrode¹¹⁷,
• Kenneth Rice¹¹⁸,
• Stephen S. Rich³⁶,
• Paul M. Ridker^34,35,
• Natalia S. Rost^9,13,
• Peter M. Rothwell¹¹⁹,
• Jerome I. Rotter^120,121,
• Tatjana Rundek¹²²,
• Ralph L. Sacco¹²²,
• Saori Sakaue^7,123,
• Michele M. Sale¹²⁴,
• Veikko Salomaa⁶³,
• Bishwa R. Sapkota¹²⁵,
• Reinhold Schmidt¹²⁶,
• Carsten O. Schmidt¹²⁷,
• Ulf Schminke¹²⁸,
• Pankaj Sharma³⁹,
• Agnieszka Slowik¹²⁹,
• Cathie L. M. Sudlow^114,115,
• Christian Tanislav¹³⁰,
• Turgut Tatlisumak^131,132,
• Kent D. Taylor^120,121,
• Vincent N. S. Thijs^133,134,
• Gudmar Thorleifsson¹¹,
• Unnur Thorsteinsdottir¹¹,
• Steffen Tiedt¹,
• Stella Trompet¹³⁵,
• Christophe Tzourio^5,136,137,
• Cornelia M. van Duijn^138,139,
• Matthew Walters¹⁴⁰,
• Nicholas J. Wareham⁸⁶,
• Sylvia Wassertheil-Smoller¹⁴¹,
• James G. Wilson¹⁴²,
• Kerri L. Wiggins¹⁰⁹,
• Qiong Yang⁴⁷,
• Salim Yusuf¹⁵,
• Najaf Amin¹⁶,
• Hugo S. Aparicio^48,183,
• Donna K. Arnett¹⁸⁴,
• John Attia¹⁸⁵,
• Alexa S. Beiser^47,48,
• Claudine Berr¹⁸⁶,
• Julie E. Buring^34,35,
• Mariana Bustamante¹⁸⁷,
• Valeria Caso¹⁸⁸,
• Yu-Ching Cheng¹⁸⁹,
• Seung Hoan Choi^48,190,
• Ayesha Chowhan^48,183,
• Natalia Cullell³¹,
• Jean-François Dartigues^191,192,
• Hossein Delavaran^95,96,
• Pilar Delgado¹⁹³,
• Marcus Dörr^194,195,
• Gunnar Engström¹⁹,
• Ian Ford¹⁹⁶,
• Wander S. Gurpreet¹⁹⁷,
• Anders Hamsten^198,199,
• Laura Heitsch²⁰⁰,
• Atsushi Hozawa²⁰¹,
• Laura Ibanez²⁰²,
• Andreea Ilinca^95,96,
• Martin Ingelsson²⁰³,
• Motoki Iwasaki²⁰⁴,
• Rebecca D. Jackson²⁰⁵,
• Katarina Jood²⁰⁶,
• Pekka Jousilahti⁶³,
• Sara Kaffashian^4,5,
• Lalit Kalra²⁰⁷,
• Masahiro Kamouchi²⁰⁸,
• Takanari Kitazono²⁰⁹,
• Olafur Kjartansson²¹⁰,
• Manja Kloss²¹¹,
• Peter J. Koudstaal²¹²,
• Jerzy Krupinski²¹³,
• Daniel L. Labovitz²¹⁴,
• Cathy C. Laurie¹¹⁸,
• Christopher R. Levi²¹⁵,
• Linxin Li²¹⁶,
• Lars Lind²¹⁷,
• Cecilia M. Lindgren^218,219,
• Vasileios Lioutas^48,220,
• Yong Mei Liu²²¹,
• Oscar L. Lopez²²²,
• Hirata Makoto²²³,
• Nicolas Martinez-Majander¹⁷⁰,
• Koichi Matsuda²²³,
• Naoko Minegishi²⁰¹,
• Joan Montaner²²⁴,
• Andrew P. Morris^225,226,
• Elena Muiño³¹,
• Martina Müller-Nurasyid^227,228,229,
• Bo Norrving^95,96,
• Soichi Ogishima²⁰¹,
• Eugenio A. Parati²³⁰,
• Leema Reddy Peddareddygari⁵⁶,
• Nancy L. Pedersen^98,231,
• Joanna Pera¹²⁹,
• Markus Perola^63,232,
• Alessandro Pezzini²³³,
• Silvana Pileggi²³⁴,
• Raquel Rabionet²³⁵,
• Iolanda Riba-Llena³⁰,
• Marta Ribasés²³⁶,
• Jose R. Romero^48,183,
• Jaume Roquer^237,238,
• Anthony G. Rudd^239,240,
• Antti-Pekka Sarin^241,242,
• Ralhan Sarju¹⁹⁷,
• Chloe Sarnowski^47,48,
• Makoto Sasaki²⁴³,
• Claudia L. Satizabal^48,183,
• Mamoru Satoh²⁴³,
• Naveed Sattar²⁴⁴,
• Norie Sawada²⁰⁴,
• Gerli Sibolt¹⁷⁰,
• Ásgeir Sigurdsson²⁴⁵,
• Albert Smith²⁴⁶,
• Kenji Sobue²⁴³,
• Carolina Soriano-Tárraga²³⁸,
• Tara Stanne²⁴⁷,
• O. Colin Stine²⁴⁸,
• David J. Stott²⁴⁹,
• Konstantin Strauch^227,250,
• Takako Takai²⁰¹,
• Hideo Tanaka^251,252,
• Kozo Tanno²⁴³,
• Alexander Teumer²⁵³,
• Liisa Tomppo¹⁷⁰,
• Nuria P. Torres-Aguila³¹,
• Emmanuel Touze^254,255,
• Shoichiro Tsugane²⁰⁴,
• Andre G. Uitterlinden²⁵⁶,
• Einar M. Valdimarsson²⁵⁷,
• Sven J. van der Lee¹⁶,
• Henry Völzke²⁵³,
• Kenji Wakai²⁵¹,
• David Weir²⁵⁸,
• Stephen R. Williams²⁵⁹,
• Charles D. A. Wolfe^239,240,
• Quenna Wong¹¹⁸,
• Huichun Xu¹⁸⁹,
• Taiki Yamaji²⁰⁴,
• Dharambir K. Sanghera^125,167,168,
• Olle Melander¹⁹,
• Christina Jern¹⁶⁹,
• Daniel Strbian^170,171,
• Israel Fernandez-Cadenas^30,31,
• W. T. Longstreth Jr^65,172,
• Arndt Rolfs¹⁷³,
• Jun Hata¹⁰⁷,
• Daniel Woo⁸²,
• Jonathan Rosand^12,13,14,
• Guillaume Pare¹⁵,
• Jemma C. Hopewell¹⁷⁴,
• Danish Saleheen¹⁷⁵,
• Kari Stefansson^11,176,
• Bradford B. Worrall¹⁷⁷,
• Steven J. Kittner³⁷,
• Sudha Seshadri^48,178,
• Myriam Fornage^74,179,
• Hugh S. Markus³,
• Joanna M. M. Howson²⁸,
• Yoichiro Kamatani^6,180,
• Stephanie Debette^4,5,
• Martin Dichgans^1,181,182,
• AFGen Consortium,
• Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium,
• International Genomics of Blood Pressure (iGEN-BP) Consortium,
• INVENT Consortium,
• STARNET,
• BioBank Japan Cooperative Hospital Group,
• COMPASS Consortium,
• EPIC-CVD Consortium,
• EPIC-InterAct Consortium,
• International Stroke Genetics Consortium (ISGC),
• METASTROKE Consortium,
• Neurology Working Group of the CHARGE Consortium,
• NINDS Stroke Genetics Network (SiGN),
• UK Young Lacunar DNA Study,
• MEGASTROKE Consortium &
• […]
• MEGASTROKE Consortium:
• - Show fewer authors

• Nature Genetics (2018)
• doi:10.1038/s41588-018-0058-3
• Download Citation
• • Genetics
  • Genome-wide association studies
  • Stroke

Received:

19 May 2017

Accepted:

08 January 2018

Published online:

12 March 2018

AbstractAbstract

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.

• Subscribe to Nature Genetics for full access:

  $59
  Subscribe

• ReadCube Access:

  $4.99 rent

  $20.00 buy

  Buy/Rent now

Additional access options:

Already a subscriber?  Log in  now or  Register  for online access.

• Login via Athens |
• Login via Shibboleth |
• Use a document delivery service |
• Purchase a site license