Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes.
- Authors
- ,
- ,
- ,
- ,
- ,
- ,
- ,
- ,
- ,
- ,
- ,
- ,
- ,
- ,
- ,
- ,
- Hieab H. H. Adams
- Hieab H. H. Adams
- Tetsuro Ago
- Tetsuro Ago
- Peter Almgren
- Peter Almgren
- Najaf Amin
- Philippe Amouyel
- Philippe Amouyel
- Christopher D. Anderson
- Christopher D. Anderson
- Hugo S. Aparicio
- Donna K. Arnett
- John Attia
- Hakan Ay
- Hakan Ay
- Traci M. Bartz
- Traci M. Bartz
- Alexa S. Beiser
- Oscar R. Benavente
- Oscar R. Benavente
- Claudine Berr
- Steve Bevan
- Steve Bevan
- Joshua C. Bis
- Johan L. M. Björkegren
- Giorgio B. Boncoraglio
- Giorgio B. Boncoraglio
- Robert D. Brown
- Robert D. Brown
- Julie E. Buring
- Mariana Bustamante
- Adam S. Butterworth
- Adam S. Butterworth
- Caty Carrera
- Caty Carrera
- Cara L. Carty
- Cara L. Carty
- Valeria Caso
- John C. Chambers
- Daniel I. Chasman
- Daniel I. Chasman
- Ganesh Chauhan
- Ganesh Chauhan
- Wei-Min Chen
- Wei-Min Chen
- Yu-Ching Cheng
- Seung Hoan Choi
- Michael Chong
- Michael Chong
- Ayesha Chowhan
- Ingrid E. Christophersen
- Mete Civelek
- Veronica Codoni
- John W. Cole
- John W. Cole
- Adolfo Correa
- Adolfo Correa
- Ioana Cotlarciuc
- Ioana Cotlarciuc
- Carlos Cruchaga
- Carlos Cruchaga
- Natalia Cullell
- John Danesh
- John Danesh
- Jean-François Dartigues
- Paul I. W. de Bakker
- Paul I. W. de Bakker
- Stephanie Debette
- Stephanie Debette
- Hossein Delavaran
- Pilar Delgado
- Marcel den Hoed
- Anita L. DeStefano
- Anita L. DeStefano
- Martin Dichgans
- Martin Dichgans
- Qing Duan
- Qing Duan
- Marcus Dörr
- Patrick T. Ellinor
- Paul Elliott
- Stefan T. Engelter
- Stefan T. Engelter
- Gunnar Engström
- Guido J. Falcone
- Guido J. Falcone
- Israel Fernandez-Cadenas
- Israel Fernandez-Cadenas
- Ian Ford
- Myriam Fornage
- Myriam Fornage
- Anne-Katrin Giese
- Anne-Katrin Giese
- Rebecca F. Gottesman
- Rebecca F. Gottesman
- Solveig Gretarsdottir
- Solveig Gretarsdottir
- Raji P. Grewal
- Raji P. Grewal
- Vilmundur Gudnason
- Vilmundur Gudnason
- Wander S. Gurpreet
- Stefan Gustafsson
- Stefan Gustafsson
- Jeffrey Haessler
- Jeffrey Haessler
- Anders Hamsten
- Tamara B. Harris
- Tamara B. Harris
- Ahamad Hassan
- Ahamad Hassan
- Jun Hata
- Jun Hata
- Aki S. Havulinna
- Aki S. Havulinna
- Jiang He
- Susan R. Heckbert
- Susan R. Heckbert
- Laura Heitsch
- Marcel den Hoed
- Elizabeth G. Holliday
- Elizabeth G. Holliday
- Jemma C. Hopewell
- Jemma C. Hopewell
- George Howard
- George Howard
- Joanna M. M. Howson
- Joanna M. M. Howson
- Atsushi Hozawa
- Fang-Chi Hsu
- Fang-Chi Hsu
- Hyacinth I. Hyacinth
- Hyacinth I. Hyacinth
- Laura Ibanez
- M. Arfan Ikram
- M. Arfan Ikram
- Andreea Ilinca
- Erik Ingelsson
- Erik Ingelsson
- Martin Ingelsson
- Marguerite R. Irvin
- Marguerite R. Irvin
- Motoki Iwasaki
- Rebecca D. Jackson
- Christina Jern
- Christina Jern
- Xueqiu Jian
- Xueqiu Jian
- Jordi Jiménez-Conde
- Jordi Jiménez-Conde
- Andrew D. Johnson
- Julie A. Johnson
- Julie A. Johnson
- Katarina Jood
- Pekka Jousilahti
- J. Wouter Jukema
- J. Wouter Jukema
- Sara Kaffashian
- Lalit Kalra
- Yoichiro Kamatani
- Yoichiro Kamatani
- Masahiro Kamouchi
- Masahiro Kanai
- Masahiro Kanai
- Norihiro Kato
- Keith L. Keene
- Keith L. Keene
- Brett M. Kissela
- Brett M. Kissela
- Takanari Kitazono
- Steven J. Kittner
- Steven J. Kittner
- Olafur Kjartansson
- Dawn O. Kleindorfer
- Dawn O. Kleindorfer
- Manja Kloss
- Jaspal S. Kooner
- Charles Kooperberg
- Charles Kooperberg
- Simon Koplev
- Peter J. Koudstaal
- Jerzy Krupinski
- Michiaki Kubo
- Michiaki Kubo
- Daniel L. Labovitz
- Leslie A. Lange
- Leslie A. Lange
- Carl D. Langefeld
- Carl D. Langefeld
- Claudia Langenberg
- Claudia Langenberg
- Lenore J. Launer
- Lenore J. Launer
- Cathy C. Laurie
- Jin-Moo Lee
- Jin-Moo Lee
- Robin Lemmens
- Robin Lemmens
- Christopher R. Levi
- Cathryn M. Lewis
- Cathryn M. Lewis
- Didier Leys
- Didier Leys
- Linxin Li
- Wei-Yu Lin
- Wei-Yu Lin
- Lars Lind
- Arne G. Lindgren
- Arne G. Lindgren
- Cecilia M. Lindgren
- Vasileios Lioutas
- Yong Mei Liu
- W. T. Longstreth
- W. T. Longstreth
- Oscar L. Lopez
- Erik Lorentzen
- Erik Lorentzen
- Steven A. Lubitz
- Patrik K. Magnusson
- Patrik K. Magnusson
- Jane Maguire
- Jane Maguire
- Hirata Makoto
- Rainer Malik
- Rainer Malik
- Ani Manichaikul
- Ani Manichaikul
- Hugh S. Markus
- Hugh S. Markus
- Nicolas Martinez-Majander
- Koichi Matsuda
- Patrick F. McArdle
- Patrick F. McArdle
- Olle Melander
- Olle Melander
- James F. Meschia
- James F. Meschia
- Naoko Minegishi
- Aniket Mishra
- Aniket Mishra
- Braxton D. Mitchell
- Braxton D. Mitchell
- Joan Montaner
- Andrew P. Morris
- Thomas H. Mosley
- Thomas H. Mosley
- Elena Muiño
- Martina Müller-Nurasyid
- Michael A. Nalls
- Michael A. Nalls
- Toshiharu Ninomiya
- Toshiharu Ninomiya
- Bo Norrving
- Soichi Ogishima
- Yukinori Okada
- Yukinori Okada
- Martin J. O’Donnell
- Martin J. O’Donnell
- Eugenio A. Parati
- Guillaume Pare
- Guillaume Pare
- Tomi Pastinen
- Leema Reddy Peddareddygari
- Nancy L. Pedersen
- Joanna Pera
- Markus Perola
- Alessandro Pezzini
- Silvana Pileggi
- Bruce M. Psaty
- Bruce M. Psaty
- Sara L. Pulit
- Sara L. Pulit
- Raquel Rabionet
- Kristiina Rannikmäe
- Kristiina Rannikmäe
- Alexander P. Reiner
- Alexander P. Reiner
- Kathryn M. Rexrode
- Kathryn M. Rexrode
- Iolanda Riba-Llena
- Marta Ribasés
- Kenneth Rice
- Kenneth Rice
- Stephen S. Rich
- Stephen S. Rich
- Paul M. Ridker
- Paul M. Ridker
- Arndt Rolfs
- Arndt Rolfs
- Jose R. Romero
- Jaume Roquer
- Jonathan Rosand
- Jonathan Rosand
- Carolina Roselli
- Natalia S. Rost
- Natalia S. Rost
- Peter M. Rothwell
- Peter M. Rothwell
- Jerome I. Rotter
- Jerome I. Rotter
- Anthony G. Rudd
- Tatjana Rundek
- Tatjana Rundek
- Loes Rutten-Jacobs
- Loes Rutten-Jacobs
- Arno Ruusalepp
- Ralph L. Sacco
- Ralph L. Sacco
- Saori Sakaue
- Saori Sakaue
- Michele M. Sale
- Michele M. Sale
- Danish Saleheen
- Danish Saleheen
- Veikko Salomaa
- Veikko Salomaa
- Dharambir K. Sanghera
- Dharambir K. Sanghera
- Bishwa R. Sapkota
- Bishwa R. Sapkota
- Muralidharan Sargurupremraj
- Muralidharan Sargurupremraj
- Antti-Pekka Sarin
- Ralhan Sarju
- Chloe Sarnowski
- Makoto Sasaki
- Claudia L. Satizabal
- Mamoru Satoh
- Naveed Sattar
- Norie Sawada
- Eric E. Schadt
- Carsten O. Schmidt
- Carsten O. Schmidt
- Reinhold Schmidt
- Reinhold Schmidt
- Ulf Schminke
- Ulf Schminke
- Sudha Seshadri
- Sudha Seshadri
- Pankaj Sharma
- Pankaj Sharma
- Gerli Sibolt
- Ásgeir Sigurdsson
- Agnieszka Slowik
- Agnieszka Slowik
- Albert Smith
- Nicholas L. Smith
- Kenji Sobue
- Carolina Soriano-Tárraga
- Tara Stanne
- Kari Stefansson
- Kari Stefansson
- O. Colin Stine
- David J. Stott
- Konstantin Strauch
- Daniel Strbian
- Daniel Strbian
- Cathie L. M. Sudlow
- Cathie L. M. Sudlow
- E. Shyong Tai
- Takako Takai
- Fumihiko Takeuchi
- Hideo Tanaka
- Christian Tanislav
- Christian Tanislav
- Kozo Tanno
- Turgut Tatlisumak
- Turgut Tatlisumak
- Kent D. Taylor
- Kent D. Taylor
- Alexander Teumer
- Vincent N. S. Thijs
- Vincent N. S. Thijs
- Gudmar Thorleifsson
- Gudmar Thorleifsson
- Unnur Thorsteinsdottir
- Unnur Thorsteinsdottir
- Steffen Tiedt
- Steffen Tiedt
- Liisa Tomppo
- Nuria P. Torres-Aguila
- Emmanuel Touze
- Matthew Traylor
- Matthew Traylor
- Stella Trompet
- Stella Trompet
- David A. Trégouët
- Shoichiro Tsugane
- Christophe Tzourio
- Christophe Tzourio
- Andre G. Uitterlinden
- Einar M. Valdimarsson
- Pim van der Harst
- Sander W. van der Laan
- Sander W. van der Laan
- Sven J. van der Lee
- Cornelia M. van Duijn
- Cornelia M. van Duijn
- Henry Völzke
- Kenji Wakai
- Matthew Walters
- Matthew Walters
- Nicholas J. Wareham
- Nicholas J. Wareham
- Sylvia Wassertheil-Smoller
- Sylvia Wassertheil-Smoller
- David Weir
- Kerri L. Wiggins
- Kerri L. Wiggins
- Stephen R. Williams
- James G. Wilson
- James G. Wilson
- Charles D. A. Wolfe
- Quenna Wong
- Daniel Woo
- Daniel Woo
- Bradford B. Worrall
- Bradford B. Worrall
- Huichun Xu
- Taiki Yamaji
- Qiong Yang
- Qiong Yang
- Salim Yusuf
- Salim Yusuf
- Publication date
- 1 January 2018
- Publisher
- Nat Genet
- Doi
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 therapySimilar works
Available Versions
Last time updated on 25/11/2020
Last time updated on 21/12/2022
Last time updated on 23/01/2018