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A Genome-Wide Association Study of Outcome After Aneurysmal Subarachnoid Haemorrhage: Discovery Analysis

Candidate gene studies have identified genetic variants associated with clinical outcomes following aneurysmal subarachnoid haemorrhage (aSAH), but no genome-wide association studies have been performed to date. Here we report the results of the discovery phase of a two-stage genome-wide meta-analys...

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Autores principales: Gaastra, Ben, Alexander, Sheila, Bakker, Mark K., Bhagat, Hemant, Bijlenga, Philippe, Blackburn, Spiros L., Collins, Malie K., Doré, Sylvain, Griessenauer, Christoph J., Hendrix, Philipp, Hong, Eun Pyo, Hostettler, Isabel C., Houlden, Henry, IIhara, Koji, Jeon, Jin Pyeong, Kim, Bong Jun, Li, Jiang, Morel, Sandrine, Nyquist, Paul, Ren, Dianxu, Ruigrok, Ynte M., Werring, David, Tapper, Will, Galea, Ian, Bulters, Diederik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10444641/
https://www.ncbi.nlm.nih.gov/pubmed/36264420
http://dx.doi.org/10.1007/s12975-022-01095-4
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author Gaastra, Ben
Alexander, Sheila
Bakker, Mark K.
Bhagat, Hemant
Bijlenga, Philippe
Blackburn, Spiros L.
Collins, Malie K.
Doré, Sylvain
Griessenauer, Christoph J.
Hendrix, Philipp
Hong, Eun Pyo
Hostettler, Isabel C.
Houlden, Henry
IIhara, Koji
Jeon, Jin Pyeong
Kim, Bong Jun
Li, Jiang
Morel, Sandrine
Nyquist, Paul
Ren, Dianxu
Ruigrok, Ynte M.
Werring, David
Tapper, Will
Galea, Ian
Bulters, Diederik
author_facet Gaastra, Ben
Alexander, Sheila
Bakker, Mark K.
Bhagat, Hemant
Bijlenga, Philippe
Blackburn, Spiros L.
Collins, Malie K.
Doré, Sylvain
Griessenauer, Christoph J.
Hendrix, Philipp
Hong, Eun Pyo
Hostettler, Isabel C.
Houlden, Henry
IIhara, Koji
Jeon, Jin Pyeong
Kim, Bong Jun
Li, Jiang
Morel, Sandrine
Nyquist, Paul
Ren, Dianxu
Ruigrok, Ynte M.
Werring, David
Tapper, Will
Galea, Ian
Bulters, Diederik
author_sort Gaastra, Ben
collection PubMed
description Candidate gene studies have identified genetic variants associated with clinical outcomes following aneurysmal subarachnoid haemorrhage (aSAH), but no genome-wide association studies have been performed to date. Here we report the results of the discovery phase of a two-stage genome-wide meta-analysis of outcome after aSAH. We identified 157 independent loci harbouring 756 genetic variants associated with outcome after aSAH (p < 1 × 10(−4)), which require validation. A single variant (rs12949158), in SPNS2, achieved genome-wide significance (p = 4.29 × 10(−8)) implicating sphingosine-1-phosphate signalling in outcome after aSAH. A large multicentre international effort to recruit samples for validation is required and ongoing. Validation of these findings will provide significant insight into the pathophysiology of outcomes after aSAH with potential implications for treatment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12975-022-01095-4.
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spelling pubmed-104446412023-08-24 A Genome-Wide Association Study of Outcome After Aneurysmal Subarachnoid Haemorrhage: Discovery Analysis Gaastra, Ben Alexander, Sheila Bakker, Mark K. Bhagat, Hemant Bijlenga, Philippe Blackburn, Spiros L. Collins, Malie K. Doré, Sylvain Griessenauer, Christoph J. Hendrix, Philipp Hong, Eun Pyo Hostettler, Isabel C. Houlden, Henry IIhara, Koji Jeon, Jin Pyeong Kim, Bong Jun Li, Jiang Morel, Sandrine Nyquist, Paul Ren, Dianxu Ruigrok, Ynte M. Werring, David Tapper, Will Galea, Ian Bulters, Diederik Transl Stroke Res Research Candidate gene studies have identified genetic variants associated with clinical outcomes following aneurysmal subarachnoid haemorrhage (aSAH), but no genome-wide association studies have been performed to date. Here we report the results of the discovery phase of a two-stage genome-wide meta-analysis of outcome after aSAH. We identified 157 independent loci harbouring 756 genetic variants associated with outcome after aSAH (p < 1 × 10(−4)), which require validation. A single variant (rs12949158), in SPNS2, achieved genome-wide significance (p = 4.29 × 10(−8)) implicating sphingosine-1-phosphate signalling in outcome after aSAH. A large multicentre international effort to recruit samples for validation is required and ongoing. Validation of these findings will provide significant insight into the pathophysiology of outcomes after aSAH with potential implications for treatment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12975-022-01095-4. Springer US 2022-10-20 2023 /pmc/articles/PMC10444641/ /pubmed/36264420 http://dx.doi.org/10.1007/s12975-022-01095-4 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research
Gaastra, Ben
Alexander, Sheila
Bakker, Mark K.
Bhagat, Hemant
Bijlenga, Philippe
Blackburn, Spiros L.
Collins, Malie K.
Doré, Sylvain
Griessenauer, Christoph J.
Hendrix, Philipp
Hong, Eun Pyo
Hostettler, Isabel C.
Houlden, Henry
IIhara, Koji
Jeon, Jin Pyeong
Kim, Bong Jun
Li, Jiang
Morel, Sandrine
Nyquist, Paul
Ren, Dianxu
Ruigrok, Ynte M.
Werring, David
Tapper, Will
Galea, Ian
Bulters, Diederik
A Genome-Wide Association Study of Outcome After Aneurysmal Subarachnoid Haemorrhage: Discovery Analysis
title A Genome-Wide Association Study of Outcome After Aneurysmal Subarachnoid Haemorrhage: Discovery Analysis
title_full A Genome-Wide Association Study of Outcome After Aneurysmal Subarachnoid Haemorrhage: Discovery Analysis
title_fullStr A Genome-Wide Association Study of Outcome After Aneurysmal Subarachnoid Haemorrhage: Discovery Analysis
title_full_unstemmed A Genome-Wide Association Study of Outcome After Aneurysmal Subarachnoid Haemorrhage: Discovery Analysis
title_short A Genome-Wide Association Study of Outcome After Aneurysmal Subarachnoid Haemorrhage: Discovery Analysis
title_sort genome-wide association study of outcome after aneurysmal subarachnoid haemorrhage: discovery analysis
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10444641/
https://www.ncbi.nlm.nih.gov/pubmed/36264420
http://dx.doi.org/10.1007/s12975-022-01095-4
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