Identification of the putative causal risk factors and biomarkers of stroke using large-scale genome-wide studies

Stroke is a complex neurological disorder, and the risk factors and genetic biomarkers associated with its development are not completely understood. This study aims to identify putative causal traits and their biomarkers that influence the risk of stroke. We leveraged genome-wide association studies (GWAS) datasets to understand potential causal genetic relationships between stroke and 1,504 complex traits via the latent causal variable (LCV) and Generalised Mendelian randomisation (GSMR) methods. Our results suggest 14 traits showing potential causal genetic effects with stroke risk (|GCP|> 0.60; FDR < 0.05). These traits include cardiovascular, metabolic, and blood clot-related traits. Using mBAT-combo, we identified genes associated with these putatively causal traits and stroke, suggesting shared genetic architectures. Colocalisation analysis showed that several of those overlapping genes were colocalised between stroke and risk traits. Functional enrichment analyses of the overlapping genes highlight the role of coagulation and complement systems, specifically prothrombin and platelet activation, as well as complement and coagulation cascades. This study suggests putative causal genetic architecture and biological pathways shared between stroke and its causal traits.