Evidence for causal effects of neuropsychiatric conditions on risk for Venous Thromboembolism: a univariable and multivariable Mendelian randomization study.

BACKGROUND: Substantial observational evidence suggests an association between neuropsychiatric conditions and Venous Thromboembolism (VTE). However, the causal relationship between these two conditions requires further investigation. Therefore, we employed a two-sample Mendelian Randomization (MR) approach to assess bidirectional causal effects between four neuropsychiatric conditions and VTE, Deep Vein Thrombosis (DVT), and Pulmonary Embolism (PE).

METHODS: Genetic variants associated with four neuropsychiatric conditions, including Schizophrenia (SCH), Major Depressive Disorder (MDD), Bipolar Disorder (BD), and Epilepsy, as well as VTE, DVT, and PE were selected. Bidirectional univariable and multivariable MR methods were applied to evaluate causal relationships among these conditions. The primary causal estimates were obtained using the Inverse Variance Weighted (IVW) method with multiplicative random effects, supplemented by MR Egger regression, weighted median, simple mode, and weighted mode. Sensitivity analysis was conducted using MR pleiotropy residual sum ,funnel plots and outlier (MR-PRESSO) method.

RESULTS: Univariable MR results showed that genetic susceptibility to MDD increases the risk of VTE and PE (VTE: OR=1.25, 95%CI: 1.08-1.46, P=0.004; PE: OR=1.36, 95%CI: 1.09-1.69, P=0.006), and PE has an adverse causal effect on MDD (OR=1.02, 95%CI: 1.00-1.04, P=0.026). Adjustment for confounders such as obesity, sleep duration, smoking, physical activity, and alcohol consumption revealed that increased genetic susceptibility to MDD is also associated with VTE and PE.

CONCLUSION: Our study suggests that genetic susceptibility to MDD may have an adverse causal effect on the risk of VTE and PE, and PE has a reverse causal effect on MDD. Prevention and early diagnosis of depression are crucial in the management of VTE and PE.