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

Authors

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 Ren
Ynte M Ruigrok
David Werring
Will Tapper
Ian Galea
Diederik Bulters

Publication Date

10-1-2023

Journal

Translational Stroke Research

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.

Keywords

Humans, Subarachnoid Hemorrhage, Genome-Wide Association Study, Longitudinal Studies, Treatment Outcome

Comments

The online version contains supplementary material available at 10.1007/s12975-022-01095-4.