The effects of coagulation factors on the risk of glioma: a two-sample bi-directional Mendelian randomization study

Abstract

Background Traditional observational studies have shown that the levels of coagulation factors can affect the risk of glioma. It is uncertain, nevertheless, whether coagulation factor levels and various glioma subtypes are causally related. The purpose of this study was to look into any bidirectional correlations between glioma risk and coagulation factor levels. Method Two-sample bi-directional Mendelian randomization (MR) analysis was carried out using openly accessible genome-wide association study (GWAS) data. The data for glioma subtypes were retrieved from an enormous-scale genetic meta-analysis compiled by GWAS data from independent European lineages of glioma, including 12,488 cases and 18,169 controls. The genetic summary data for 10 coagulation factors were retrieved from different GWAS results conducted in participants of European ancestry (up to 21758 participants), involving prothrombin time (PT), activated protein C(APC), von Willebrand factor (VWF), plasmin, a disintegrin-like and metalloproteinase with thrombospondin motifs 13 (ADAMTS13), factor VII (FVII), factor VIII (FVIII), factor X (FVX), plasminogen activator inhibitor-1 (PAI-1), and thrombomodulin (TM). Weighted median estimation (WME), MR-Egger regression, and inverse variance weighting (IVW) were the MR analysis approaches that were applied. IVW was selected as the main research method. Furthermore, the Benjamini-Hochberg false discovery rate (FDR) correction and sensitivity analyses were carried out. Results We discovered a potential relationship between genetically predicted FVII levels and a higher risk of glioblastoma (GBM) (OR = 1.07, 95% CI: 1.01–1.14, P = 0.03). Our results also suggested that genetically predicted plasma PAI-1 level was negatively associated with the incidence of all glioma (OR = 0.85, 95%CI: 0.73–0.98, P = 0.03) and non-GBM (OR = 0.77, 95%CI: 0.63–0.92, P = 0.01). In addition, a suggestively negative correlation between genetically predicted PT level and the risk of GBM (OR = 0.72, 95%CI: 0.53–0.98, P = 0.04) was discovered. Conversely, there was insufficient evidence of a significant causal association of any examined glioma with coagulation factors. Conclusions Our findings suggest that coagulation factors may be important indicators for glioma treatment and may be involved in the pathophysiology of gliomas.