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

被引：6

作者：

Gaastra, Ben ^{[1
,2
]}

Alexander, Sheila ^{[3
]}

Bakker, Mark K. ^{[4
]}

Bhagat, Hemant ^{[5
]}

Bijlenga, Philippe ^{[6
]}

Blackburn, Spiros ^{[7
]}

Collins, Malie K. ^{[8
]}

Dore, Sylvain ^{[9
,10
,11
,12
,13
]}

Griessenauer, Christoph ^{[14
,15
]}

Hendrix, Philipp ^{[14
,16
]}

Hong, Eun Pyo ^{[17
]}

Hostettler, Isabel C. ^{[18
]}

Houlden, Henry ^{[18
]}

IIhara, Koji ^{[19
]}

Jeon, Jin Pyeong ^{[17
,20
]}

Kim, Bong Jun ^{[17
]}

Kumar, Munish ^{[5
]}

Morel, Sandrine ^{[6
,21
]}

Nyquist, Paul ^{[22
,23
,24
,25
]}

Ren, Dianxu ^{[3
]}

Ruigrok, Ynte M. ^{[4
]}

Werring, David ^{[18
]}

Galea, Ian ^{[1
]}

Bulters, Diederik ^{[2
]}

Tapper, Will ^{[1
]}

机构：

[1] Univ Southampton, Fac Med, Clin Neurosci Clin & Expt Sci, Southampton SO17 1BJ, Hants, England

[2] Univ Hosp Southampton, Wessex Neurol Ctr, Dept Neurosurg, Southampton SO16 6YD, Hants, England

[3] Univ Pittsburgh, Sch Nursing, 3500 Victoria St, Pittsburgh, PA 15261 USA

[4] Univ Med Ctr Utrecht, Brain Ctr, Dept Neurol, Heidelberlaan 100, NL-3584 CX Utrecht, Netherlands

[5] Postgrad Inst Med Educ & Res PGIMER, Dept Anaesthesia & Intens Care, Div Neuroanaesthesia, Chandigarh, India

[6] Geneva Univ Hosp, Fac Med, Dept Clin Neurosci, Neurosurg Div, Geneva, Switzerland

[7] Univ Texas Houston, Hlth Sci Ctr, Houston, TX USA

[8] Geisinger Commonwealth Sch Med, Scranton, PA USA

[9] Univ Florida, Coll Med, Ctr Translat Res Neurodegenerat Dis, Dept Anesthesiol,McKnight Brain Inst, Gainesville, FL USA

[10] Univ Florida, Coll Med, Ctr Translat Res Neurodegenerat Dis, Dept Neurol,McKnight Brain Inst, Gainesville, FL USA

[11] Univ Florida, Coll Med, Ctr Translat Res Neurodegenerat Dis, Dept Psychiat,McKnight Brain Inst, Gainesville, FL USA

[12] Univ Florida, Coll Med, Ctr Translat Res Neurodegenerat Dis, Dept Pharmaceut,McKnight Brain Inst, Gainesville, FL USA

[13] Univ Florida, Coll Med, Ctr Translat Res Neurodegenerat Dis, Dept Neurosci,McKnight Brain Inst, Gainesville, FL USA

[14] Geisinger, Dept Neurosurg, Danville, PA USA

[15] Paracelsus Med Univ, Dept Neurosurg, Christian Doppler Klin, Salzburg, Austria

[16] Saarland Univ, Dept Neurosurg, Med Ctr, Homburg, Germany

[17] Hallym Univ, Inst New Frontier Res, Coll Med, Chunchon, South Korea

[18] UCL, Stroke Res Ctr, Inst Neurol, London, England

[19] Natl Cerebral & Cardiovasc Ctr Hosp, 6-1 Kishibe Shimmachi, Suita, Osaka, Japan

[20] Hallym Univ, Dept Neurosurg, Coll Med, Chunchon, South Korea

[21] Univ Geneva, Fac Med, Dept Pathol & Immunol, Geneva, Switzerland

[22] Johns Hopkins Sch Med, Dept Neurol, Baltimore, MD 21287 USA

[23] Johns Hopkins Sch Med, Dept Anesthesia Crit Care Med, Baltimore, MD 21287 USA

[24] Johns Hopkins Sch Med, Dept Neurosurg, Baltimore, MD 21287 USA

[25] Johns Hopkins Sch Med, Dept Gen Internal Med, Baltimore, MD 21287 USA

来源：

TRANSLATIONAL STROKE RESEARCH | 2022年 / 13卷 / 04期

基金：

欧洲研究理事会;

关键词：

Subarachnoid haemorrhage; Stroke; Outcome assessment; Health care; Genetics; Medical; CEREBRAL VASOSPASM; POLYMORPHISM; GENOTYPE; ISCHEMIA; INJURY; ALLELE; TIME;

D O I：

10.1007/s12975-021-00978-2

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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.

引用

页码：565 / 576

页数：12

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