Inflammatory cytokines and venous thrombosis bidirectional causal correlations: A Mendelian randomization study

Previous studies have demonstrated that venous thromboembolism (VTE) is characterized by the interplay between inflammatory mechanisms and coagulation cascades. However, these observational studies may be susceptible to biases such as reverse causation and unmeasured confounding, leaving the causal relationship between inflammation and VTE unclear. To better understand this relationship, we conducted a 2-sample Mendelian randomization (MR) study, employing a bidirectional MR analysis using publicly available genome-wide association statistics. To enhance the reliability of our findings, we utilized 5 distinct approaches (inverse variance weighted, MR-Egger, weighted median, simple mode, and weighted mode) for MR analysis and performed rigorous tests for heterogeneity and horizontal pleiotropy. The study included 4185 individuals diagnosed with pulmonary embolism (PE) and 4576 cases of deep vein thrombosis (DVT). The forward MR analysis indicated a positive correlation between elevated levels of granulocyte colony stimulating factor (odds ratio [OR]: 1.36, P = 6.15 × 10-4) and interleukin-2 (OR: 1.17, P = .023) with an increased susceptibility to PE. Additionally, Eotaxin (OR: 1.18, P = 5.92 × 10-3) was positively correlated with an elevated risk of DVT. Conversely, the reverse MR analysis revealed no discernible causal link between PE, DVT, and 41 inflammatory cytokines. Our study concludes that granulocyte colony stimulating factor and interleukin-2 are risk factors for PE, while Eotaxin is a risk factor for DVT. Furthermore, reverse analyses confirmed that neither PE nor DVT serve as risk factors for elevated levels of the 41 inflammatory cytokines. Our research furnishes novel evidence underpinning a causal relationship between inflammatory cytokines and VTE. This newfound knowledge may offer invaluable insights for the development of early - screening methods and intervention therapies for VTE in the future.