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

Ben Gaastra, Sheila Alexander, Mark K. Bakker, Hemant Bhagat, Philippe Bijlenga, Spiros L. Blackburn, Malie K. Collins, Sylvain Doré, Christoph J. Griessenauer, Philipp Hendrix, Eun Pyo Hong, Isabel C. Hostettler, Henry Houlden, Koji IIhara, Jin Pyeong Jeon, Bong Jun Kim, Jiang Li, Sandrine Morel, Paul Nyquist, Dianxu RenYnte M. Ruigrok, David Werring, Will Tapper*, Ian Galea, Diederik Bulters

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

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.

Original languageEnglish
Pages (from-to)681-687
Number of pages7
JournalTranslational Stroke Research
Volume14
Issue number5
DOIs
Publication statusPublished - Oct 2023

Keywords

  • Genetics, Medical
  • Outcome assessment, Health care
  • Stroke
  • Subarachnoid haemorrhage

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