Genome-wide association meta-analysis of functional outcome after ischemic stroke

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Fältnamn	Indikatorer	Metadata
000		05608naa a2200793 4500
001		oai:gup.ub.gu.se/280143
003		SwePub
008		240528s2019 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
024	7	a https://gup.ub.gu.se/publication/2801432 URI
024	7	a https://doi.org/10.1212/wnl.00000000000071382 DOI
040		a (SwePub)gu
041		a eng
042		9 SwePub
072	7	a ref2 swepub-contenttype
072	7	a art2 swepub-publicationtype
100	1	a Soderholm, M.4 aut
245	1 0	a Genome-wide association meta-analysis of functional outcome after ischemic stroke
264		c 2019-02-22
264	1	b Ovid Technologies (Wolters Kluwer Health),c 2019
520		a 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 x 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 x 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.
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Neurovetenskaper0 (SwePub)301052 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Neurosciences0 (SwePub)301052 hsv//eng
653		a neuronal differentiation
653		a sod1 expression
653		a genetic-factors
653		a tie2
653		a receptor
653		a angiopoietin-1
653		a identification
653		a netrin-4
653		a recovery
653		a genotype
653		a damage
700	1	a Pedersen, Annie,d 1981u Gothenburg University,Göteborgs universitet,Institutionen för biomedicin,Institute of Biomedicine4 aut0 (Swepub:gu)xpeder
700	1	a Lorentzen, Erik,d 1974u Gothenburg University,Göteborgs universitet,Core Facilities, Bioinformatics,Core Facilities, Bioinformatics4 aut0 (Swepub:gu)xjacer
700	1	a Stanne, Tara M,d 1979u Gothenburg University,Göteborgs universitet,Institutionen för biomedicin,Institute of Biomedicine4 aut0 (Swepub:gu)xmcdta
700	1	a Bevan, S.4 aut
700	1	a Olsson, Maja,d 1975u Gothenburg University,Göteborgs universitet,Institutionen för biomedicin,Institute of Biomedicine4 aut0 (Swepub:gu)xolmaj
700	1	a Cole, J. W.4 aut
700	1	a Fernandez-Cadenas, I.4 aut
700	1	a Hankey, G. J.4 aut
700	1	a Jimenez-Conde, J.4 aut
700	1	a Jood, Katarina,d 1966u Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience4 aut0 (Swepub:gu)xjooka
700	1	a Lee, J. M.4 aut
700	1	a Lemmens, R.4 aut
700	1	a Levi, C.4 aut
700	1	a Mitchell, B. D.4 aut
700	1	a Norrving, B.4 aut
700	1	a Rannikmae, K.4 aut
700	1	a Rost, N. S.4 aut
700	1	a Rosand, J.4 aut
700	1	a Rothwell, P. M.4 aut
700	1	a Scott, R.4 aut
700	1	a Strbian, D.4 aut
700	1	a Sturm, J. W.4 aut
700	1	a Sudlow, C.4 aut
700	1	a Traylor, M.4 aut
700	1	a Thijs, V.4 aut
700	1	a Tatlisumak, Turgutu Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience4 aut0 (Swepub:gu)xtatlt
700	1	a Woo, D.4 aut
700	1	a Worrall, B. B.4 aut
700	1	a Maguire, J. M.4 aut
700	1	a Lindgren, A.4 aut
700	1	a Jern, Christina,d 1962u Gothenburg University,Göteborgs universitet,Institutionen för biomedicin,Institute of Biomedicine4 aut0 (Swepub:gu)xjerch
710	2	a Göteborgs universitetb Institutionen för biomedicin4 org
773	0	t Neurologyd : Ovid Technologies (Wolters Kluwer Health)g 92:12q 92:12x 0028-3878x 1526-632X
856	4	u https://n.neurology.org/content/neurology/92/12/e1271.full.pdf
856	4 8	u https://gup.ub.gu.se/publication/280143
856	4 8	u https://doi.org/10.1212/wnl.0000000000007138

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