Mendelian Randomization Study Does Not Support a Bidirectional Link between Atherosclerosis and Venous...

Area of Science:

• Cardiovascular Science
• Genetics
• Epidemiology

Background:

• Observational studies suggest a link between atherosclerosis and venous thromboembolism (VTE), but findings are conflicting.
• Establishing a causal relationship between coronary heart disease (CHD) and VTE, deep venous thrombosis (DVT), and pulmonary embolism (PE) is crucial.

Approach:

• Utilized Mendelian randomization (MR) analyses to investigate bidirectional causality between CHD and VTE, DVT, and PE.
• Employed genetic instruments from large-scale consortia (CARDIoGRAMplusC4D and FinnGen) with robust statistical methods, including inverse-variance weighted meta-analysis and complementary MR techniques.
• Adjusted for potential confounders like body mass index in multivariable MR analyses.

Key Points:

• MR analyses revealed no significant causal relationship between genetically predicted VTE, DVT, or PE and CHD.
• Conversely, genetically predicted CHD did not demonstrate a causal effect on VTE, DVT, or PE.
• No evidence of pleiotropic bias was detected, and heterogeneity was addressed using a random-effect model.

Conclusions:

• This study provides strong evidence against a causal association between coronary heart disease and venous thromboembolism.
• The findings suggest that arterial and venous thrombotic events may be driven by independent pathophysiological mechanisms.