Title
Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes
Date Issued
01 April 2018
Access level
open access
Resource Type
journal article
Author(s)
Malik R.
Chauhan G.
Traylor M.
Sargurupremraj M.
Okada Y.
Mishra A.
Rutten-Jacobs L.
Giese A.K.
Van Der Laan S.W.
Gretarsdottir S.
Anderson C.D.
Chong M.
Adams H.H.H.
Ago T.
Almgren P.
Amouyel P.
Ay H.
Bartz T.M.
Benavente O.R.
Bevan S.
Boncoraglio G.B.
Brown R.D.
Butterworth A.S.
Carrera C.
Carty C.L.
Chasman D.I.
Chen W.M.
Cole J.W.
Correa A.
Cotlarciuc I.
Cruchaga C.
Danesh J.
De Bakker P.I.W.
Destefano A.L.
Den Hoed M.
Duan Q.
Engelter S.T.
Falcone G.J.
Gottesman R.F.
Grewal R.P.
Gudnason V.
Gustafsson S.
Haessler J.
Harris T.B.
Hassan A.
Havulinna A.S.
Heckbert S.R.
Holliday E.G.
Howard G.
Hsu F.C.
Hyacinth H.I.
Ikram M.A.
Ingelsson E.
Irvin M.R.
Jian X.
Jiménez-Conde J.
Johnson J.A.
Jukema J.W.
Kanai M.
Keene K.L.
Kissela B.M.
Kleindorfer D.O.
Kooperberg C.
Kubo M.
Lange L.A.
Langefeld C.D.
Langenberg C.
Launer L.J.
Lee J.M.
Lemmens R.
Leys D.
Lewis C.M.
Lin W.Y.
Lindgren A.G.
Lorentzen E.
Magnusson P.K.
Maguire J.
Manichaikul A.
McArdle P.F.
Meschia J.F.
Mitchell B.D.
Mosley T.H.
Nalls M.A.
Ninomiya T.
O'Donnell M.J.
Psaty B.M.
Pulit S.L.
Rannikmäe K.
Reiner A.P.
Rexrode K.M.
Rice K.
Rich S.S.
Ridker P.M.
Rost N.S.
Rothwell P.M.
Rotter J.I.
Rundek T.
Sacco R.L.
Sakaue S.
Sale M.M.
Publisher(s)
Nature Publishing Group
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.
Start page
524
End page
537
Volume
50
Issue
4
Language
English
OCDE Knowledge area
Genética, Herencia
Sistema cardiaco, Sistema cardiovascular
Neurociencias
Scopus EID
2-s2.0-85043463446
PubMed ID
Source
Nature Genetics
ISSN of the container
10614036
Sponsor(s)
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. 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. 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.
Sources of information:
Directorio de Producción Científica
Scopus