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  • 2018 (1)

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  • Amouyel, Philippe
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Article

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

by Rainer Malik; Ganesh Chauhan; Matthew Traylor; Muralidharan Sargurupremraj; Yukinori Okada; Aniket Mishra; Loes Rutten-Jacobs; Anne-Katrin Giese; Sander W. van der Laan; Solveig Gretarsdottir; Christopher D. Anderson; Michael Chong; Hieab H. H. Adams; Tetsuro Ago; Peter Almgren; Philippe Amouyel; Hakan Ay; Traci M Bartz; Oscar R. Benavente; Steve Bevan; Giorgio B. Boncoraglio; Robert D. Brown; Adam S. Butterworth; Caty Carrera; Cara L. Carty; Daniel I. Chasman; Wei-Min Chen; John W. Cole; Adolfo Correa; Ioana Cotlarciuc; Carlos Cruchaga; John Danesh; Paul I. W. de Bakker; Anita L. DeStefano; Marcel den Hoed; Qing Duan; Stefan T. Engelter; Guido J. Falcone; Rebecca F. Gottesman; Raji P. Grewal; Vilmunder Gudnason; Stefan Gustafsson; Jeffery Haessler; Tamara B Harris; Ahamad Hassan; Aki S. Havulinna; Susan R. Heckbert; Elizabeth G. Holliday; George Howard; Fang-Chi Hsu; Hyacinth Hyacinth; M. Arfan Ikram; Erik Ingelsson; Marguerite R. Irvin; Xuequi Jian; Jordi Jimenez-Conde; Julie A. Johnson; J. Wouter Jukema; Masahiro Kanai; Keith L. Keene; Brett M. Kissela; Dawn O. Kleindorfer; Charles Kooperberg; Michiaki Kubo; Leslie A. Lange; Carl D. Langefeld; Claudia Langenberg; Lenore J. Launer; Jin-Moo Lee; Robin Lemmens; Didier Leys; Cathryn M. Lewis; Wei-Yun Lin; Arne G. Lindgren; Erik Lorentzen; Patrik K. Magnusson; Jane Maguire; Ani Manichaikul; Patrick F. McArdle; James F. Meschia; Braxton D. Mitchell; Thomas H. Mosley

2018

Subjects
  • Biology, Genetics
  • Health Sciences, Medicine and Surgery
  • File Download
  • View Abstract

Abstract:Close

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.
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