Figure 6.

Contextualization of Mendelian randomization (MR) associations with canonical coagulation cascade pathways. The visualized canonical pathways were derived from the Kyoto Encyclopedia of Genes and Genomes pathway database and supporting literature and should not be considered exhaustive. Proteins are displayed according to their abbreviated gene name. We excluded Serpin proteins for visualization purposes. The text color corresponds to findings from associations of genetically proxied perturbation of coagulation cascade proteins with ischemic stroke and venous thromboembolism (VTE): gray for proteins without an available genetic proxy; black for genetically proxied proteins not associated with VTE or ischemic stroke; bold black for genetically proxied proteins only associated with VTE; and bold red for genetically proxied proteins associated with ischemic stroke (all of which except for urokinase were also associated with VTE). We note that the anticoagulant mechanisms of γ′ fibrinogen remain incompletely understood. Additionally, the figure depicts the canonical role of endothelial-bound PROCR (protein C receptor); however, our study investigated effects of soluble PROCR, which may act through different mechanisms. CAD indicates coronary artery disease; CES, cardioembolic stroke; FV, factor V; HMWK, high-molecular-weight kininogen; IS, ischemic stroke; LAAS, large artery atherosclerotic stroke; PROC, protein C; PROS, protein S; TAFI, thrombin-activatable fibrinolysis inhibitor; TFPI, tissue factor pathway inhibitor; THBD, thrombomodulin; tPA, tissue-type plasminogen activator; UPA, urokinase-type plasminogen activator; and VWF, von Willebrand Factor. *Consistent results in sensitivity analyses.