Genome-wide association study links COL6A6 and PIK3R4 to delayed cerebral ischaemia
Clicks: 1
ID: 315033
2026
Article Quality & Performance Metrics
Overall Quality
Not rated
Combines reader engagement with the AI quality analysis. This
article has not been analysed, so there is no overall score —
reader engagement is measured and shown alongside.
Reader Engagement
0.0
/100
1 views
0 readers
AI Quality Assessment
Not analyzed
Readership in this journal
Ranked #350 of 375 articles by views in Brain research
Most read
Least read
Bar heights use a square-root scale. Only the 120 most-read articles are drawn; the journal has 375 in total.
Mint this article as an NFT
Not yet mintedCreate a permanent, verifiable on-chain record of this article on the Scimatic Network. The NFT is held in your Journament account, and you can withdraw it to your own wallet at any time.
5
SUSD
one-off · no wallet required
Abstract
Abstract Delayed cerebral ischaemia (DCI) is a major determinant of poor clinical outcome after aneurysmal subarachnoid haemorrhage (aSAH), but its underlying mechanisms are not fully understood. We aimed to perform a genome-wide association study (GWAS) in aSAH patients with and without DCI. We conducted a multicentre study of European ancestry within the International Stroke Genetics Consortium with two stages: Stage 1 (n = 1,085; four centres) and Stage 2 (n = 801; one centre). A GWAS meta-analysis was performed across both stages. We then examined whether variants associated with DCI were linked to differences in gene expression (expression quantitative trait loci, eQTLs) or DNA methylation (methylation quantitative trait loci, mQTLs) and validated the methylation findings in an aSAH cohort with available DNA methylation data (n = 344). We performed complementary postGWAS analysis in order to promote biological interpretation of the genome-wide findings, including the genetic overlap with ischaemic stroke and intracranial aneurysm (ruptured and unruptured) using publicly available published GWAS summary statistics. Among 1,879 patients with DCI data, the prevalence of DCI was 22.8% (428/1,879). In the meta-analysis across both stages, we identified one genome-wide significant variant, rs7636350 (Chr3:130328911:T:C), associated with an increased risk of DCI (additive OR 1.75 [95% CI 1.43–2.13], P=4.47×10⁻⁸). This variant mapped near the COL6A6 and PIK3R4 genes. Functional annotation revealed one significant eQTL for PIK3R4 and one mQTL for cg23181900, located within COL6A6. Hypermethylation at cg23181900 was associated with DCI in a cohort with DNA methylation data (logFC=0.016, 95% CI 0.002–0.032; P=0.0317). Genetic correlation analyses showed a marginal correlation with ischaemic stroke due to large artery atherosclerosis (r=0.172; P=0.0508) and a higher correlation with intracranial aneurysm (r=0.341; P=0.002). We identified a genome-wide significant locus associated with DCI after aSAH, implicating COL6A6 and PIK3R4. We additionally identified an mQTL at cg23181900, suggesting a regulatory link at this locus. These findings enhance our understanding of DCI pathophysiology and support further studies to clarify causality and determine whether these pathways may inform future therapeutic strategies.
| Reference Key |
openalex_W7162469690
Use this key to autocite in the manuscript while using
SciMatic Manuscript Manager or Thesis Manager
|
|---|---|
| Authors | Joan Jiménez-Baladó, Marc Arreaza-Baena, Mark K Bakker, Ynte M Ruigrok, M Vallverdu-Prats, Angel Ois, Adrià Macias-Gómez, Isabel Fernández-Pérez, Daniel Guisado-Alonso, Ana Rodríguez-Campello, Eva Giralt-Steinhauer, Jordi Jiménez-Conde, Philippe Bijlenga, Sandrine Morel, Behnam Rezai Jahromi, Mika Niemelä, David J Werring, Isabel C. Hostettler, Elisa Cuadrado-Godia |
| Journal | Brain research |
| Year | 2026 |
| DOI |
10.1093/brain/awag188
|
| URL | |
| Keywords | Keywords not found |
Citations
No citations found. To add a citation, contact the admin at info@scimatic.org
Comments
No comments yet. Be the first to comment on this article.