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Genome-wide associa...
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Söderholm, MartinLund University,Lunds universitet,Kardiovaskulär forskning - epidemiologi,Forskargrupper vid Lunds universitet,Cardiovascular Research - Epidemiology,Lund University Research Groups,Skåne University Hospital
(author)
Genome-wide association meta-analysis of functional outcome after ischemic stroke
- Article/chapterEnglish2019
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LIBRIS-ID:oai:lup.lub.lu.se:dc82c1c5-38e2-4468-99ed-a261e61c871d
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https://lup.lub.lu.se/record/dc82c1c5-38e2-4468-99ed-a261e61c871dURI
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https://doi.org/10.1212/WNL.0000000000007138DOI
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Language:English
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Summary in:English
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Subject category:art swepub-publicationtype
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Subject category:ref swepub-contenttype
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OBJECTIVE: To discover common genetic variants associated with poststroke outcomes using a genome-wide association (GWA) study. METHODS: The study comprised 6,165 patients with ischemic stroke from 12 studies in Europe, the United States, and Australia included in the GISCOME (Genetics of Ischaemic Stroke Functional Outcome) network. The primary outcome was modified Rankin Scale score after 60 to 190 days, evaluated as 2 dichotomous variables (0-2 vs 3-6 and 0-1 vs 2-6) and subsequently as an ordinal variable. GWA analyses were performed in each study independently and results were meta-analyzed. Analyses were adjusted for age, sex, stroke severity (baseline NIH Stroke Scale score), and ancestry. The significance level was p < 5 × 10-8. RESULTS: We identified one genetic variant associated with functional outcome with genome-wide significance (modified Rankin Scale scores 0-2 vs 3-6, p = 5.3 × 10-9). This intronic variant (rs1842681) in the LOC105372028 gene is a previously reported trans-expression quantitative trait locus for PPP1R21, which encodes a regulatory subunit of protein phosphatase 1. This ubiquitous phosphatase is implicated in brain functions such as brain plasticity. Several variants detected in this study demonstrated suggestive association with outcome (p < 10-5), some of which are within or near genes with experimental evidence of influence on ischemic stroke volume and/or brain recovery (e.g., NTN4, TEK, and PTCH1). CONCLUSIONS: In this large GWA study on functional outcome after ischemic stroke, we report one significant variant and several variants with suggestive association to outcome 3 months after stroke onset with plausible mechanistic links to poststroke recovery. Future replication studies and exploration of potential functional mechanisms for identified genetic variants are warranted.
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Pedersen, AnnieUniversity of Gothenburg
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Lorentzen, ErikUniversity of Gothenburg
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Stanne, Tara M.University of Gothenburg
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Bevan, SteveUniversity of Lincoln
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Olsson, MajaUniversity of Gothenburg
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Cole, John W.University of Maryland, Baltimore
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Fernandez-Cadenas, IsraelVall d'Hebron University Hospital
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Hankey, Graeme J.University of Western Australia, Crawley
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Jimenez-Conde, JordiAutonomous University of Barcelona
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Jood, KatarinaUniversity of Gothenburg
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Lee, Jin MooWashington University in St. Louis
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Lemmens, RobinUniversity Hospitals Leuven
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Levi, ChristopherUniversity of Technology Sydney
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Mitchell, Braxton D.University of Maryland, Baltimore
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Norrving, BoLund University,Lunds universitet,Neurologi, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Klinisk strokeforskning,Forskargrupper vid Lunds universitet,Stroke policy och kvalitetsregisterforskning,Neurology, Lund,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Clinical Stroke Research Group,Lund University Research Groups,Stroke policy and quality register research,Skåne University Hospital(Swepub:lu)neur-bno
(author)
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Rannikmäe, KristiinaUniversity of Edinburgh
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Rost, Natalia S.Harvard Medical School
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Rosand, JonathanHarvard Medical School
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Rothwell, Peter M.University of Oxford
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Scott, RodneyUniversity of Technology Sydney
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Strbian, DanielHelsinki University Central Hospital
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Sturm, Jonathan W.University of Newcastle
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Sudlow, CathieUniversity of Edinburgh
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Traylor, MatthewUniversity of Cambridge
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Thijs, VincentUniversity of Melbourne
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Tatlisumak, TurgutUniversity of Gothenburg
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Woo, DanielUniversity of Cincinnati
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Worrall, Bradford B.University of Virginia
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Maguire, Jane M.University of Technology Sydney
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Lindgren, ArneLund University,Lunds universitet,Neurologi, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Klinisk strokeforskning,Forskargrupper vid Lunds universitet,Neurology, Lund,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Clinical Stroke Research Group,Lund University Research Groups,Skåne University Hospital(Swepub:lu)neur-ali
(author)
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Jern, ChristinaUniversity of Gothenburg
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Kardiovaskulär forskning - epidemiologiForskargrupper vid Lunds universitet
(creator_code:org_t)
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International Stroke Genetics Consortium, the NINDS-SiGN Consortium, and the Genetics of Ischaemic Stroke Functional Outcome (GISCOME) Network
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In:Neurology92:12, s. 1271-12831526-632X
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Söderholm, Marti ...
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Pedersen, Annie
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Lorentzen, Erik
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Stanne, Tara M.
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Bevan, Steve
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Olsson, Maja
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Cole, John W.
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Fernandez-Cadena ...
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Hankey, Graeme J ...
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Jimenez-Conde, J ...
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Jood, Katarina
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Lee, Jin Moo
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Lemmens, Robin
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Levi, Christophe ...
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Mitchell, Braxto ...
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Norrving, Bo
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Rannikmäe, Krist ...
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Rost, Natalia S.
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Rosand, Jonathan
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Rothwell, Peter ...
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Scott, Rodney
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Strbian, Daniel
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Sturm, Jonathan ...
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Sudlow, Cathie
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Traylor, Matthew
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Thijs, Vincent
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Tatlisumak, Turg ...
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Woo, Daniel
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Worrall, Bradfor ...
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Maguire, Jane M.
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Lindgren, Arne
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Jern, Christina
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