biostudies-literatureWu XNatural Science Foundation of Chongqing MunicipalityChongqing Municipal Science and Health Joint Medical Research ProjectNational Natural Science Foundation of ChinaInternational Postdoctoral Exchange Fellowship Program296https://www.ebi.ac.uk/biostudies/studies/S-EPMC12153161biostudies-literatureUnknown20(1)<h4>Background</h4>Current 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.<h4>Methods</h4>SS-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 identOrphanet journal of rare diseasesCausal relationships between alterations in shear stress-related genes and aneurysmal subarachnoid hemorrhage.PMC121531612022CQBSHGJPY0052025QNXM0218240156382471305CSTB2023NSCQ-BHX0204Sheng WLi JXie YZhang MYe FDai YNiu XWu XfalseCausal relationships between alterations in shear stress-related genes and aneurysmal subarachnoid hemorrhage.<h4>Background</h4>Current 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.<h4>Methods</h4>SS-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 ident2025-01-01T00:00:00Z2025 Jun2026-06-02T02:35:06.525Z2026-05-25T03:07:06.44ZS-EPMC121531614050073910.1186/s13023-025-03784-3