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

Publication

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

Journal Paper/Review - Jan 6, 2022

Gaastra Ben, Alexander Sheila, Bakker Mark K, Bhagat Hemant, Bijlenga Philippe, Blackburn Spiros, 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, Kumar Munish, Morel Sandrine, Nyquist Paul, Ren Dianxu, Ruigrok Ynte M, Werring David, Galea Ian, Bulters Diederik, Tapper Will

Citation

Gaastra B, Alexander S, Bakker M, Bhagat H, Bijlenga P, Blackburn S, Collins M, Doré S, Griessenauer C, Hendrix P, Hong E, Hostettler I, Houlden H, IIhara K, Jeon J, Kim B, Kumar M, Morel S, Nyquist P, Ren D, Ruigrok Y, Werring D, Galea I, Bulters D, Tapper W. Genome-Wide Association Study of Clinical Outcome After Aneurysmal Subarachnoid Haemorrhage: Protocol. Transl Stroke Res 2022; 13:565-576.

Type

Journal Paper/Review (English)

Journal

Transl Stroke Res 2022; 13

Publication Date

Jan 6, 2022

Issn Electronic

1868-601X

Pages

565-576

Brief description/objective

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.