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Author Notes:

Correspondence and requests for materials should be addressed to S.D. or M.D. : stephanie.debette@u-bordeaux.frmartin.dichgans@med.uni-muenchen.de

See publication for full list of authors.

These authors contributed equally: Rainer Malik, Ganesh Chauhan, Matthew Traylor, Muralidharan Sargurupremraj and Yukinori Okada.

These authors jointly supervised this work: Kari Stefansson, Bradford B. Worrall, Steven J. Kittner, Sudha Seshadri, Myriam Fornage, Hugh S. Markus, Joanna M. M. Howson, Yoichiro Kamatani, Stephanie Debette and Martin Dichgans.

See publication for full list of author contributions.

The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute or the National Institute of Neurological Disorders and Stroke.

S. Gretarsdottir, G.T., U.T., and K.S. are all employees of deCODE Genetics/Amgen, Inc.

M.A.N. is an employee of Data Tecnica International.

S.A.L. receives sponsored research support from Bayer HealthCare, Biotronik, and Boehringer Ingelheim, and has consulted for St. Jude Medical and Quest Diagnostics.

E.I. is a scientific advisor for Precision Wellness, Cellink and Olink Proteomics for work unrelated to the present project.

B.M.P. serves on the DSMB of a clinical trial funded by Zoll LifeCor and on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson.

The remaining authors have no disclosures.

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Research Funding:

P.T.E. is the PI on a grant from Bayer HealthCare to the Broad Institute, focused on the genetics and therapeutics of atrial fibrillation.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Genetics & Heredity
  • SMALL-VESSEL DISEASE
  • WHITE-MATTER HYPERINTENSITIES
  • CORONARY-ARTERY-DISEASE
  • HUMAN GENETIC-VARIATION
  • SUDDEN CARDIAC DEATH
  • ATRIAL-FIBRILLATION
  • ISCHEMIC-STROKE
  • COMPLEX TRAITS
  • SUSCEPTIBILITY LOCI
  • HEMORRHAGIC STROKE

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

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Journal Title:

Nature Genetics

Volume:

Volume 50, Number 4

Publisher:

, Pages 524-+

Type of Work:

Article | Post-print: After Peer Review

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.

Copyright information:

© 2018 The Author(s).

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