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Genome-wide association study of clinical outcome after aneurysmal subarachnoid haemorrhage: protocol

Genome-wide association study of clinical outcome after aneurysmal subarachnoid haemorrhage: protocol
Genome-wide association study of clinical outcome after aneurysmal subarachnoid haemorrhage: protocol
Aneurysmal subarachnoid haemorrhage (aSAH) results in persistent clinical deficits which prevent survivors from returning to normal daily functioning. Only a small fraction of the variation in clinical outcome following aSAH is explained by known clinical, demographic and imaging variables; meaning additional unknown factors must play a key role in clinical outcome. There is a growing body of evidence that genetic variation is important in determining outcome following aSAH. Understanding genetic determinants of outcome will help to improve prognostic modelling, stratify patients in clinical trials and target novel strategies to treat this devastating disease. This protocol details a two-stage genome-wide association study to identify susceptibility loci for clinical outcome after aSAH using individual patient-level data from multiple international cohorts. Clinical outcome will be assessed using the modified Rankin Scale or Glasgow Outcome Scale at 1–24 months. The stage 1 discovery will involve meta-analysis of individual-level genotypes from different cohorts, controlling for key covariates. Based on statistical significance, supplemented by biological relevance, top single nucleotide polymorphisms will be selected for replication at stage 2. The study has national and local ethical approval. The results of this study will be rapidly communicated to clinicians, researchers and patients through open-access publication(s), presentation(s) at international conferences and via our patient and public network.
Genetics, Health care, Medical, Outcome assessment, Stroke, Subarachnoid haemorrhage
1868-601X
565-576
Gaastra, Ben
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Alexander, Sheila
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Bakker, Mark K.
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Bhagat, Hemant
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Bijlenga, Philippe
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Blackburn, Spiros
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Collins, Malie K.
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Doré, Sylvain
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Griessenauer, Christoph
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Hendrix, Philipp
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Hong, Eun Pyo
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Hostettler, Isabel C.
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Houlden, Henry
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IIhara, Koji
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Jeon, Jin Pyeong
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Kim, Bong Jun
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Kumar, Munish
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Morel, Sandrine
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Nyquist, Paul
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Ren, Dianxu
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Ruigrok, Ynte M.
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Werring, David
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Galea, Ian
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Bulters, Diederik
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Tapper, Will
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Gaastra, Ben
c7b7f371-706b-4d59-9150-94e8f254e205
Alexander, Sheila
8a9ea84a-93d5-4b15-8182-b8e64ae38cc7
Bakker, Mark K.
9d4329de-a731-4b13-8087-5772fc81ab36
Bhagat, Hemant
474008a7-1f97-4fc0-a348-05c727d456f4
Bijlenga, Philippe
a902aaa8-1776-47c3-8be0-96e08f99fb02
Blackburn, Spiros
e2bfd052-b403-4c15-9422-626c260ddfd7
Collins, Malie K.
d446df8c-5dad-4732-9243-138a899244e2
Doré, Sylvain
004e2fdb-3bf4-4143-b905-fd4e16f85cf5
Griessenauer, Christoph
3f983fd7-36f9-4ddb-b8f4-545c131071f5
Hendrix, Philipp
ed9170d3-83d5-4ad0-a48b-94b9e789534f
Hong, Eun Pyo
be02f781-7328-4061-97e7-ce54e3215369
Hostettler, Isabel C.
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Houlden, Henry
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IIhara, Koji
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Jeon, Jin Pyeong
4ac824d8-af55-43a2-810b-1144211d64dc
Kim, Bong Jun
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Kumar, Munish
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Morel, Sandrine
47155706-d8ac-449b-ab3f-9a30dcd235f1
Nyquist, Paul
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Ren, Dianxu
1b2b6a0a-4465-49a0-a23a-48c59d2d0a97
Ruigrok, Ynte M.
36542439-1c84-4e9a-97c3-bf9591cf8120
Werring, David
0caabc8a-8597-4f08-9189-e8a6e6a213a6
Galea, Ian
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Bulters, Diederik
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Tapper, Will
9d5ddc92-a8dd-4c78-ac67-c5867b62724c

Gaastra, Ben, Alexander, Sheila, Bakker, Mark K., Bhagat, Hemant, Bijlenga, Philippe, Blackburn, Spiros, Collins, Malie K., Doré, Sylvain, Griessenauer, Christoph, Hendrix, Philipp, Hong, Eun Pyo, Hostettler, Isabel C., Houlden, Henry, IIhara, Koji, Jeon, Jin Pyeong, Kim, Bong Jun, Kumar, Munish, Morel, Sandrine, Nyquist, Paul, Ren, Dianxu, Ruigrok, Ynte M., Werring, David, Galea, Ian, Bulters, Diederik and Tapper, Will (2022) Genome-wide association study of clinical outcome after aneurysmal subarachnoid haemorrhage: protocol. Translational Stroke Research, 13 (4), 565-576. (doi:10.1007/s12975-021-00978-2).

Record type: Article

Abstract

Aneurysmal subarachnoid haemorrhage (aSAH) results in persistent clinical deficits which prevent survivors from returning to normal daily functioning. Only a small fraction of the variation in clinical outcome following aSAH is explained by known clinical, demographic and imaging variables; meaning additional unknown factors must play a key role in clinical outcome. There is a growing body of evidence that genetic variation is important in determining outcome following aSAH. Understanding genetic determinants of outcome will help to improve prognostic modelling, stratify patients in clinical trials and target novel strategies to treat this devastating disease. This protocol details a two-stage genome-wide association study to identify susceptibility loci for clinical outcome after aSAH using individual patient-level data from multiple international cohorts. Clinical outcome will be assessed using the modified Rankin Scale or Glasgow Outcome Scale at 1–24 months. The stage 1 discovery will involve meta-analysis of individual-level genotypes from different cohorts, controlling for key covariates. Based on statistical significance, supplemented by biological relevance, top single nucleotide polymorphisms will be selected for replication at stage 2. The study has national and local ethical approval. The results of this study will be rapidly communicated to clinicians, researchers and patients through open-access publication(s), presentation(s) at international conferences and via our patient and public network.

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Accepted/In Press date: 13 December 2021
e-pub ahead of print date: 6 January 2022
Published date: August 2022
Additional Information: Funding Information: BG is funded by the Royal College of Surgeons, Society of British Neurological Surgeons and Barrow Foundation, and the Institute for Life Sciences, University of Southampton. DJW, HH and IH received funding for recruitment to the GOSH study and genotyping from the Stroke Association and the UCLH NIHR Biomedical Research Centre. SA received funding for data and sample collection from the National Institute of Nursing Research (R01NR004339). YR received funding from the Netherlands Cardiovascular Research Initiative: An initiative with the support of the Dutch Heart Foundation, CVON2015-08 ERASE, and from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (PRYSM, grant agreement No. 852173). PB and SM received funding for the AneuX project from SystemsX.ch, which was evaluated by the Swiss National Science Foundation. SB is supported by NIH Grant (K23NS106054). SD is funded by the National Institute of Neurological Disorders and Stroke (1R56NS116076-01A1 & 1R21NA110008-01A1) and The Assistant Secretary of Defense for Health Affairs endorsed by the Department of Defense (W81XWH1910606) Publisher Copyright: © 2021, The Author(s).
Keywords: Genetics, Health care, Medical, Outcome assessment, Stroke, Subarachnoid haemorrhage

Identifiers

Local EPrints ID: 454945
URI: http://eprints.soton.ac.uk/id/eprint/454945
ISSN: 1868-601X
PURE UUID: 44638076-d5b1-4641-984a-885636d47551
ORCID for Ben Gaastra: ORCID iD orcid.org/0000-0002-7517-6882
ORCID for Ian Galea: ORCID iD orcid.org/0000-0002-1268-5102
ORCID for Diederik Bulters: ORCID iD orcid.org/0000-0001-9884-9050
ORCID for Will Tapper: ORCID iD orcid.org/0000-0002-5896-1889

Catalogue record

Date deposited: 02 Mar 2022 17:44
Last modified: 13 Jan 2023 03:01

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Contributors

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

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