Genome-wide association meta-analysis of functional outcome after ischemic stroke
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 St...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2019 |
| País: | España |
| Institución: | Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau) |
| Repositorio: | r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau |
| OAI Identifier: | oai:iibsantpau.fundanetsuite.com:p2890 |
| Acceso en línea: | https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=2890 http://ddd.uab.cat/record/223195 |
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Genome-wide association meta-analysis of functional outcome after ischemic strokeSoderholm, MPedersen, ALorentzen, EStanne, TMBevan, SOlsson, MCole, JWFernandez-Cadenas, IHankey, GJJimenez-Conde, JJood, KLee, JMLemmens, RLevi, CMitchell, BDNorrving, BRannikmae, KRost, NSRosand, JRothwell, PMScott, RStrbian, DSturm, JWSudlow, CTraylor, MThijs, VTatlisumak, TWoo, DWorrall, BBMaguire, JMLindgren, AJern, CInt Stroke Genetics ConsortiumNINDS-SIGN ConsortiumGenetics Ischaemic Stroke FunctObjective 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.LIPPINCOTT WILLIAMS & WILKINS2019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=2890http://ddd.uab.cat/record/223195NEUROLOGYISSN: 00283878ISSNe: 1526632Xreponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pauinstname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)Inglésinfo:eu-repo/semantics/openAccessoai:iibsantpau.fundanetsuite.com:p28902026-06-14T12:41:47Z |
| dc.title.none.fl_str_mv |
Genome-wide association meta-analysis of functional outcome after ischemic stroke |
| title |
Genome-wide association meta-analysis of functional outcome after ischemic stroke |
| spellingShingle |
Genome-wide association meta-analysis of functional outcome after ischemic stroke Soderholm, M |
| title_short |
Genome-wide association meta-analysis of functional outcome after ischemic stroke |
| title_full |
Genome-wide association meta-analysis of functional outcome after ischemic stroke |
| title_fullStr |
Genome-wide association meta-analysis of functional outcome after ischemic stroke |
| title_full_unstemmed |
Genome-wide association meta-analysis of functional outcome after ischemic stroke |
| title_sort |
Genome-wide association meta-analysis of functional outcome after ischemic stroke |
| dc.creator.none.fl_str_mv |
Soderholm, M Pedersen, A Lorentzen, E Stanne, TM Bevan, S Olsson, M Cole, JW Fernandez-Cadenas, I Hankey, GJ Jimenez-Conde, J Jood, K Lee, JM Lemmens, R Levi, C Mitchell, BD Norrving, B Rannikmae, K Rost, NS Rosand, J Rothwell, PM Scott, R Strbian, D Sturm, JW Sudlow, C Traylor, M Thijs, V Tatlisumak, T Woo, D Worrall, BB Maguire, JM Lindgren, A Jern, C Int Stroke Genetics Consortium NINDS-SIGN Consortium Genetics Ischaemic Stroke Funct |
| author |
Soderholm, M |
| author_facet |
Soderholm, M Pedersen, A Lorentzen, E Stanne, TM Bevan, S Olsson, M Cole, JW Fernandez-Cadenas, I Hankey, GJ Jimenez-Conde, J Jood, K Lee, JM Lemmens, R Levi, C Mitchell, BD Norrving, B Rannikmae, K Rost, NS Rosand, J Rothwell, PM Scott, R Strbian, D Sturm, JW Sudlow, C Traylor, M Thijs, V Tatlisumak, T Woo, D Worrall, BB Maguire, JM Lindgren, A Jern, C Int Stroke Genetics Consortium NINDS-SIGN Consortium Genetics Ischaemic Stroke Funct |
| author_role |
author |
| author2 |
Pedersen, A Lorentzen, E Stanne, TM Bevan, S Olsson, M Cole, JW Fernandez-Cadenas, I Hankey, GJ Jimenez-Conde, J Jood, K Lee, JM Lemmens, R Levi, C Mitchell, BD Norrving, B Rannikmae, K Rost, NS Rosand, J Rothwell, PM Scott, R Strbian, D Sturm, JW Sudlow, C Traylor, M Thijs, V Tatlisumak, T Woo, D Worrall, BB Maguire, JM Lindgren, A Jern, C Int Stroke Genetics Consortium NINDS-SIGN Consortium Genetics Ischaemic Stroke Funct |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| description |
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. |
| publishDate |
2019 |
| dc.date.none.fl_str_mv |
2019 |
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info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
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article |
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publishedVersion |
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https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=2890 http://ddd.uab.cat/record/223195 |
| url |
https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=2890 http://ddd.uab.cat/record/223195 |
| dc.language.none.fl_str_mv |
Inglés |
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Inglés |
| dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess |
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openAccess |
| dc.publisher.none.fl_str_mv |
LIPPINCOTT WILLIAMS & WILKINS |
| publisher.none.fl_str_mv |
LIPPINCOTT WILLIAMS & WILKINS |
| dc.source.none.fl_str_mv |
NEUROLOGY ISSN: 00283878 ISSNe: 1526632X reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau instname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau) |
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Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau) |
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r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau |
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r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau |
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