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A Genome-Wide Association Study of Outcome After Aneurysmal Subarachnoid Haemorrhage: Discovery Analysis

Candidate gene studies have identified genetic variants associated with clinical outcomes following aneurysmal subarachnoid haemorrhage (aSAH), but no genome-wide association studies have been performed to date. Here we report the results of the discovery phase of a two-stage genome-wide meta-analys...

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Detalles Bibliográficos
Autores principales: Gaastra, Ben, Alexander, Sheila, Bakker, Mark K., Bhagat, Hemant, Bijlenga, Philippe, Blackburn, Spiros L., 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, Li, Jiang, Morel, Sandrine, Nyquist, Paul, Ren, Dianxu, Ruigrok, Ynte M., Werring, David, Tapper, Will, Galea, Ian, Bulters, Diederik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10444641/
https://www.ncbi.nlm.nih.gov/pubmed/36264420
http://dx.doi.org/10.1007/s12975-022-01095-4
Descripción
Sumario:Candidate gene studies have identified genetic variants associated with clinical outcomes following aneurysmal subarachnoid haemorrhage (aSAH), but no genome-wide association studies have been performed to date. Here we report the results of the discovery phase of a two-stage genome-wide meta-analysis of outcome after aSAH. We identified 157 independent loci harbouring 756 genetic variants associated with outcome after aSAH (p < 1 × 10(−4)), which require validation. A single variant (rs12949158), in SPNS2, achieved genome-wide significance (p = 4.29 × 10(−8)) implicating sphingosine-1-phosphate signalling in outcome after aSAH. A large multicentre international effort to recruit samples for validation is required and ongoing. Validation of these findings will provide significant insight into the pathophysiology of outcomes after aSAH with potential implications for treatment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12975-022-01095-4.