TY - JOUR
T1 - Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes
AU - Neurology Working Group of the CHARGE Consortium
AU - NINDS Stroke Genetics Network (SiGN)
AU - UK Young Lacunar DNA Study
AU - MEGAST ROKE Consortium
AU - AFGen Consortium
AU - Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium
AU - International Genomics of Blood Pressure (iGEN-BP) Consortium
AU - INVENT Consortium
AU - STA RNET BioBank Japan Cooperative Hospital Group
AU - COMPASS Consortium
AU - EPIC-CVD Consortium
AU - EPIC-InterAct Consortium
AU - International Stroke Genetics Consortium (ISGC)
AU - METAST ROKE Consortium
AU - Malik, Rainer
AU - Chauhan, Ganesh
AU - Traylor, Matthew
AU - Sargurupremraj, Muralidharan
AU - Okada, Yukinori
AU - Mishra, Aniket
AU - Rutten-Jacobs, Loes
AU - Giese, Anne Katrin
AU - Van Der Laan, Sander W.
AU - Gretarsdottir, Solveig
AU - Anderson, Christopher D.
AU - Chong, Michael
AU - Adams, Hieab H.H.
AU - Ago, Tetsuro
AU - Almgren, Peter
AU - Amouyel, Philippe
AU - Ay, Hakan
AU - Bartz, Traci M.
AU - Benavente, Oscar R.
AU - Bevan, Steve
AU - Boncoraglio, Giorgio B.
AU - Brown, Robert D.
AU - Butterworth, Adam S.
AU - Carrera, Caty
AU - Carty, Cara L.
AU - Chasman, Daniel I.
AU - Chen, Wei Min
AU - Cole, John W.
AU - Correa, Adolfo
AU - Cotlarciuc, Ioana
AU - Cruchaga, Carlos
AU - Danesh, John
AU - De Bakker, Paul I.W.
AU - Destefano, Anita L.
AU - Den Hoed, Marcel
AU - Duan, Qing
AU - Engelter, Stefan T.
AU - Falcone, Guido J.
AU - Gottesman, Rebecca F.
AU - Grewal, Raji P.
AU - Gudnason, Vilmundur
AU - Gustafsson, Stefan
AU - Haessler, Jeffrey
AU - Harris, Tamara B.
AU - Hassan, Ahamad
AU - Havulinna, Aki S.
AU - Ninomiya, Toshiharu
AU - Hata, Jun
AU - Kamouchi, Masahiro
AU - Kitazono, Takanari
N1 - Funding Information:
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.
Publisher Copyright:
© 2018 The Author(s).
PY - 2018/4/1
Y1 - 2018/4/1
N2 - 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.
AB - 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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U2 - 10.1038/s41588-018-0058-3
DO - 10.1038/s41588-018-0058-3
M3 - Article
C2 - 29531354
AN - SCOPUS:85043463446
SN - 1061-4036
VL - 50
SP - 524
EP - 537
JO - Nature genetics
JF - Nature genetics
IS - 4
ER -