Scientific article
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English

Genome-Wide Association Study of Clinical Outcome After Aneurysmal Subarachnoid Haemorrhage: Protocol

Published inTranslational stroke research, vol. 13, no. 4, p. 565-576
Publication date2022-01-06
First online date2022-01-06
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.

Keywords
  • Genetics
  • Health care
  • Medical
  • Outcome assessment
  • Stroke
  • Subarachnoid haemorrhage
Funding
  • Royal College of Surgeons of England
  • Society of British Neurological Surgeons
  • Barrow Neurological Foundation
  • Institute for Life Sciences, University of Southampton
  • Stroke Association
  • UCLH Biomedical Research Centre
  • National Institute of Nursing Research [R01NR004339]
  • Netherlands Cardiovascular Research Initiative [CVON2015-08 ERASE]
  • SystemsX.ch [NA]
  • National Institutes of Health [K23NS106054]
  • NINR NIH HHS [R01 NR004339]
  • European Commission - Early recognition of intracranial aneurysms to PRevent aneurYSMal subarachnoid hemorrhage [852173]
Citation (ISO format)
GAASTRA, Ben et al. Genome-Wide Association Study of Clinical Outcome After Aneurysmal Subarachnoid Haemorrhage: Protocol. In: Translational stroke research, 2022, vol. 13, n° 4, p. 565–576. doi: 10.1007/s12975-021-00978-2
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Additional URL for this publicationhttps://link.springer.com/10.1007/s12975-021-00978-2
Journal ISSN1868-4483
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