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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. Jr.* ; 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.I.* ; Havulinna, A.S.* ; Heckbert, S.R.* ; Dichgans, M.* ; MEGASTROKE Consortium (Strauch, K.) ; 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.* ; MEGASTROKE Consortium (Müller-Nurasyid, M.)

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

Nat. Genet. 50, 524-537 (2018)

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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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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

ISSN (print) / ISBN 1061-4036

e-ISSN 1546-1718

Journal Nature Genetics

Quellenangaben Volume: 50, Issue: 4, Pages: 524-537

Publisher Nature Publishing Group

Publishing Place New York, NY

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Genetic Epidemiology (IGE)