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

Ben Gaastra; Sheila Alexander; Mark K. Bakker; Hemant Bhagat; Philippe Bijlenga; Spiros L. Blackburn; Malie K. Collins; Sylvain Doré; Christoph J. Griessenauer; Philipp Hendrix; Eun Pyo Hong; Isabel C. Hostettler; Henry Houlden; Koji IIhara; Jin Pyeong Jeon; Bong Jun Kim; Jiang Li; Sandrine Morel; Paul Nyquist; Dianxu Ren; Ynte M. Ruigrok; David Werring; Will Tapper; Ian Galea; Diederik Bulters

doi:10.1007/s12975-022-01095-4

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

Ben Gaastra, Sheila Alexander, Mark K. Bakker, Hemant Bhagat, Philippe Bijlenga, Spiros L. Blackburn, Malie K. Collins, Sylvain Doré, Christoph J. Griessenauer, Philipp Hendrix, Eun Pyo Hong, Isabel C. Hostettler, Henry Houlden, Koji IIhara, Jin Pyeong Jeon, Bong Jun Kim, Jiang Li, Sandrine Morel, Paul Nyquist, Dianxu RenYnte M. Ruigrok, David Werring, Will Tapper, Ian Galea, Diederik Bulters

School of Medicine

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English (US)
Pages (from-to)	681-687
Number of pages	7
Journal	Translational Stroke Research
Volume	14
Issue number	5
DOIs	https://doi.org/10.1007/s12975-022-01095-4
State	Published - Oct 2023

Keywords

Genetics, Medical
Outcome assessment, Health care
Stroke
Subarachnoid haemorrhage

ASJC Scopus subject areas

Clinical Neurology
Cardiology and Cardiovascular Medicine
General Neuroscience

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Gaastra, B., Alexander, S., Bakker, M. K., Bhagat, H., Bijlenga, P., Blackburn, S. L., Collins, M. K., Doré, S., Griessenauer, C. J., Hendrix, P., Hong, E. P., Hostettler, I. C., Houlden, H., IIhara, K., Jeon, J. P., Kim, B. J., Li, J., Morel, S., Nyquist, P., ... Bulters, D. (2023). A Genome-Wide Association Study of Outcome After Aneurysmal Subarachnoid Haemorrhage: Discovery Analysis. Translational Stroke Research, 14(5), 681-687. https://doi.org/10.1007/s12975-022-01095-4

Gaastra, B, Alexander, S, Bakker, MK, Bhagat, H, Bijlenga, P, Blackburn, SL, Collins, MK, Doré, S, Griessenauer, CJ, Hendrix, P, Hong, EP, Hostettler, IC, Houlden, H, IIhara, K, Jeon, JP, Kim, BJ, Li, J, Morel, S, Nyquist, P, Ren, D, Ruigrok, YM, Werring, D, Tapper, W, Galea, I & Bulters, D 2023, 'A Genome-Wide Association Study of Outcome After Aneurysmal Subarachnoid Haemorrhage: Discovery Analysis', Translational Stroke Research, vol. 14, no. 5, pp. 681-687. https://doi.org/10.1007/s12975-022-01095-4

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title = "A Genome-Wide Association Study of Outcome After Aneurysmal Subarachnoid Haemorrhage: Discovery Analysis",

abstract = "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.",

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doi = "10.1007/s12975-022-01095-4",

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AU - Gaastra, Ben

AU - Alexander, Sheila

AU - Bakker, Mark K.

AU - Bhagat, Hemant

AU - Bijlenga, Philippe

AU - Blackburn, Spiros L.

AU - Collins, Malie K.

AU - Doré, Sylvain

AU - Griessenauer, Christoph J.

AU - Hendrix, Philipp

AU - Hong, Eun Pyo

AU - Hostettler, Isabel C.

AU - Houlden, Henry

AU - IIhara, Koji

AU - Jeon, Jin Pyeong

AU - Kim, Bong Jun

AU - Li, Jiang

AU - Morel, Sandrine

AU - Nyquist, Paul

AU - Ren, Dianxu

AU - Ruigrok, Ynte M.

AU - Werring, David

AU - Tapper, Will

AU - Galea, Ian

AU - Bulters, Diederik

PY - 2023/10

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N2 - 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.

AB - 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.

KW - Genetics, Medical

KW - Outcome assessment, Health care

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KW - Subarachnoid haemorrhage

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

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Keywords

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