학술논문

Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes
Document Type
Author
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. Q.Jimenez-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, Erik, 1974; 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.Rannikmae, 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.Salomaa, V.Sapkota, B. R.Schmidt, R.Schmidt, C. O.Schminke, U.Sharma, P.Slowik, A.Sudlow, C. L. M.Tanislav, C.Tatlisumak, TurgutTaylor, K. D.Thijs, V. N. S.Thorleifsson, G.Thorsteinsdottir, U.Tiedt, S.Trompet, S.Tzourio, C.van Duijn, C. M.Walters, M.Wareham, N. J.Wassertheil-Smoller, S.Wilson, J. G.Wiggins, K. L.Yang, Q.Yusuf, S.Bis, J. C.Pastinen, T.Ruusalepp, A.Schadt, E. E.Koplev, S.Bjorkegren, J. L. M.Codoni, V.Civelek, M.Smith, N. L.Tregouet, D. A.Christophersen, I. E.Roselli, C.Lubitz, S. A.Ellinor, P. T.Tai, E. S.Kooner, J. S.Kato, N.He, J.van der Harst, P.Elliott, P.Chambers, J. C.Takeuchi, F.Johnson, A. D.Sanghera, D. K.Melander, O.Jern, Christina, 1962; Strbian, D.Fernandez-Cadenas, I.Longstreth, W. T.Rolfs, A.Hata, J.Woo, D.Rosand, J.Pare, G.Hopewell, J. C.Saleheen, D.Stefansson, K.Worrall, B. B.Kittner, S. J.Seshadri, S.Fornage, M.Markus, H. S.Howson, J. M. M.Kamatani, Y.Debette, S.Dichgans, M.A. FGen Consortium; Cohorts Heart Aging Res Genomic; Int Genomics Blood Pressure iGEN; INVENT, A. FGen Consortium; Cohorts Heart Aging Res Genomic; Int Genomics Blood Pressure iGEN; INVENT
Source
Nature Genetics. 50(D, Munich, Germany. [Chauhan, Ganesh] Indian Inst Sci, Ctr Brain Res, Bangalore, Karnataka, India. [Chauhan, Ganesh; Sargurupremraj, Muralidharan; Mishra, Aniket; Tzourio, Christophe; Debette, [Traylor, Matthew; Rutten-Jacobs, Loes; Markus, Hugh S.] Univ Cambridge, Div Clin Neurosci, Stroke [Sargurupremraj, Muralidharan; Mishra, Aniket; Debette, Stephanie] Bordeaux Univ Hosp, Inst [Okada, Yukinori; Kanai, Masahiro; Kamatani, Yoichiro] RIKEN Ctr Integrat Med Sci, Lab Stat Anal, [Okada, Yukinori; Kanai, Masahiro; Sakaue, Saori] Osaka Univ, Grad Sch Med, Dept Stat Genet, Osaka, [Okada, Yukinori] Osaka Univ, Immunol Frontier Res Ctr WPI IFReC, Lab Stat Immunol, Suita, Osaka, [Giese, Anne-Katrin; Rost, Natalia S.] Harvard Med Sch, MGH, Dept Neurol, Boston, MA USA. [van der Laan, Sander W.] Univ Utrecht, Univ Med Ctr Utrecht, Div Heart & Lungs, Lab Expt Cardiol,Dept [Gretarsdottir, Solveig; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Stefansson, Kari] DeCODE Genet [Anderson, Christopher D.; Rosand, Jonathan] MGH, Ctr Genom Med, Boston, MA USA. [Anderson, Christopher D.; Ay, Hakan; Rost, Natalia S.; Rosand, Jonathan] MGH, J Philip Kistler Stroke [Anderson, Christopher D.; Rosand, Jonathan] Broad Inst, Program Med & Populat Genet, Cambridge)
Subject
Medical Genetics
Medicinsk genetik
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
Language
English
ISSN
1061-4036
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 sub-types. 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.