Genome-Wide Association Study of Clinical Outcome After Aneurysmal Subarachnoid Haemorrhage: Protocol.
Genome-Wide Association Study of Clinical Outcome After Aneurysmal Subarachnoid Haemorrhage: Protocol.
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DOI：
10.1007/s12975-021-00978-2
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发表时间：
2022-08
影响因子：
6.9
通讯作者：
Tapper, Will
中科院分区：
文献类型：
--
作者：
Gaastra, Ben;Alexander, Sheila;Bakker, Mark K.;Bhagat, Hemant;Bijlenga, Philippe;Blackburn, Spiros;Collins, Malie K.;Dore, 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;Tapper, Will
动脉瘤性蛛网膜下腔出血(ASAH)导致持续的临床缺陷，使幸存者无法恢复正常的日常功能。ASAH后临床结果的变化只有一小部分可以由已知的临床、人口学和影像变量解释；这意味着其他未知因素必须在临床结果中发挥关键作用。越来越多的证据表明，遗传变异在决定ASAH预后方面起着重要作用。了解预后的遗传决定因素将有助于改进预后建模，在临床试验中对患者进行分层，并针对治疗这种毁灭性疾病的新策略。该方案详细介绍了一项分两个阶段的全基因组关联研究，以确定ASAH后临床结果的易感基因，使用来自多个国际队列的单个患者水平的数据。临床结果将在1-24个月时使用改良的Rankin量表或格拉斯哥结果量表进行评估。第一阶段的发现将涉及对来自不同队列的个体水平的基因类型进行荟萃分析，控制关键协变量。基于统计学意义，辅以生物相关性，在第二阶段将选择最重要的单核苷酸多态进行复制。这项研究得到了国家和地方的伦理批准。这项研究的结果将通过开放获取出版物(S)、在国际会议上发表(S)以及通过我们的患者和公共网络迅速传达给临床医生、研究人员和患者。网上版载有补充材料，可在10.1007/s12975-021-00978-2查阅。
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. The online version contains supplementary material available at 10.1007/s12975-021-00978-2.
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影响因子：
2.5
作者：
Gallek MJ;Conley YP;Sherwood PR;Horowitz MB;Kassam A;Alexander SA
通讯作者：
Alexander SA
影响因子：
7
作者：
Boyle AP;Hong EL;Hariharan M;Cheng Y;Schaub MA;Kasowski M;Karczewski KJ;Park J;Hitz BC;Weng S;Cherry JM;Snyder M
通讯作者：
Snyder M
影响因子：
30.8
作者：
Kircher, Martin;Witten, Daniela M.;Jain, Preti;O'Roak, Brian J.;Cooper, Gregory M.;Shendure, Jay
通讯作者：
Shendure, Jay
影响因子：
48
作者：
Kirkpatrick, Peter J.;Turner, Carole L.;Collaborators, S. T. A. S. H.
通讯作者：
Collaborators, S. T. A. S. H.
DOI：
10.1126/science.1262110
发表时间：
2015-05-08
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
GTEx Consortium
通讯作者：
GTEx Consortium