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Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes
Univ Hosp, LMU Munich, Inst Stroke & Dementia Res ISD, Munich, Germany.
Indian Inst Sci, Ctr Brain Res, Bangalore, Karnataka, India;Univ Bordeaux, Bordeaux Populat Hlth Res Ctr, INSERM, U1219, Bordeaux, France.
Univ Cambridge, Div Clin Neurosci, Stroke Res Grp, Cambridge, England.
Univ Bordeaux, Bordeaux Populat Hlth Res Ctr, INSERM, U1219, Bordeaux, France;Bordeaux Univ Hosp, Inst Neurodegenerat Dis, Dept Neurol, Bordeaux, France;NUI Galway, Dept Med, Clin Res Facil, Galway, Ireland.
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2018 (engelsk)Inngår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 50, nr 4, s. 524-537Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

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.

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NATURE PUBLISHING GROUP , 2018. Vol. 50, nr 4, s. 524-537
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URN: urn:nbn:se:uu:diva-352708DOI: 10.1038/s41588-018-0058-3ISI: 000429529300013PubMedID: 29531354OAI: oai:DiVA.org:uu-352708DiVA, id: diva2:1215091
Tilgjengelig fra: 2018-06-07 Laget: 2018-06-07 Sist oppdatert: 2018-06-07bibliografisk kontrollert

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