The Causality between Diabetes with Venous Thromboembolism: A Bidirectional Two-sample Mendelian Randomization Study.

BACKGROUND: Diabetes was considered as a risk factor for venous thromboembolism (VTE), but conflicting findings have been reported from observational studies. This study aimed at investigating the causal associations of type 1 and type 2 diabetes with VTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE).

METHODS: We designed a bidirectional two-sample Mendelian randomization (MR) analysis by using summary-level data from non-overlapped and large genome-wide association studies performed in European individuals. Inverse variance weighting with multiplicative random effect method was used to obtain the primary causal estimates, and weighted median and weighted mode, and MR egger regression were replenished as sensitive analyses to test the robustness of the results.

RESULTS: We found no significant causal effects of type 1 diabetes on VTE (OR: 0.98, 95% CI: 0.96-1.00, P=0.043), DVT (OR: 0.98, 95% CI: 0.95-1.00, P=0.102) and PE (OR: 0.98, 95% CI: 0.96-1.01, P=0.160). Similarly, no significant associations of type 2 diabetes with VTE (OR:0.97, 95% CI: 0.91-1.03, P=0.291), DVT (OR:0.96, 95% CI: 0.89-1.03, P=0.255) and PE (OR:0.97, 95% CI: 0.90-1.04, P=0.358) were also observed. Results from multivariate MR analysis consistent with the findings in univariate analysis. In the other direction, the results showed no significant causal effects of VTE on type 1 and type 2 diabetes.

CONCLUSION: This MR analysis demonstrated no significant causal associations of type 1 and type 2 diabetes with VTE in both directions, in conflicting with previous observational study reporting positive association, which provided clues for understanding the underlying pathogenesis of diabetes and VTE.