ArticleOrphanet journal of rare diseases2025
Causal relationships between alterations in shear stress-related genes and aneurysmal subarachnoid hemorrhage.
Article in Orphanet journal of rare diseases, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
Abstract
backgroundCurrent management of aneurysmal subarachnoid hemorrhage (aSAH) poses significant challenges, with emerging evidence implicating alterations in shear stress (SS) as critical in disease pathogenesis. However, the causal relationships and underlying molecular mechanisms remain elusive. This study aimed to elucidate the causal association of key SS-related genes with aSAH.
methodsSS-related genes were curated from the GeneCards database and transcriptomic datasets responsive to SS conditions. Expression quantitative trait loci (eQTLs) associated with these genes were identified as instrumental variables. An integrative analysis of genome-wide association study data for aSAH with eQTLs was conducted using bidirectional two-sample Mendelian randomization (MR) to identify SS-related genes causally linked to aSAH. Additionally, expression levels of identified genes were compared between ruptured and unruptured aneurysm walls. Functional assessments of these genes in vascular endothelial cells were also performed.
resultsWe identified 209 SS-related genes potentially implicated in aSAH pathogenesis. Using 599 eQTLs correlated with these genes as instrumental variables, MR analysis revealed that KCNN4 (OR = 0.83, 95% CI: 0.73-0.94) and UGCG (OR = 1.62, 95% CI: 1.07-2.48) were significantly associated with aSAH. Furthermore, RNA-sequencing data demonstrated elevated expression of KCNN4 and UGCG in ruptured intracranial aneurysms compared to unruptured ones. Functional experiments using siRNA-mediated knockdown in HUVECs showed that siKCNN4 increased cell proliferation and disrupted endothelial barriers, while siUGCG enhanced tube formation ability but reduced migration.
conclusionsOur findings suggest a causal relationship between alterations in SS-related genes and aSAH. Specifically, KCNN4 and UGCG emerge as potential biomarkers critical in the disease progression of aSAH. These insights contribute to a better understanding of the molecular basis of aSAH and may guide future therapeutic strategies targeting SS-related pathways.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.