IL-1β Signaling, Obesity, and Venous Thromboembolism: A Mendelian Randomization Study

Area of Science:

• Genetics
• Immunology
• Cardiovascular Medicine

Background:

• Anticoagulation is standard for Venous Thromboembolism (VTE) but increases bleeding risk.
• Interleukin-1 beta (IL-1β) pathway's role in VTE, particularly with obesity-related inflammation, is under-researched.
• Obesity is a known risk factor for VTE due to chronic inflammation.

Purpose of the Study:

• To investigate the causal relationship between IL-1β signaling, obesity, and VTE.
• To explore the mediating role of obesity in the IL-1β pathway's effect on VTE.
• To assess the association between IL-1β signaling and obesity-related traits with VTE risk.

Main Methods:

• Two-sample, two-step Mendelian randomization (MR) was employed.
• Genetic variants associated with IL-1β gene expression and neutrophil count served as instruments for IL-1β signaling.
• Obesity traits included body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR); VTE outcomes were deep vein thrombosis (DVT) and pulmonary embolism (PE).

Main Results:

• Decreased IL-1β signaling showed a significant association with reduced risk of PE (OR = 0.06).
• Body mass index (BMI) was associated with both IL-1β signaling and PE risk.
• BMI significantly mediated the effect of the IL-1β pathway on PE, accounting for 2.78% of the total effect.

Conclusions:

• A decreased IL-1β signaling is associated with a lower risk of PE.
• Body mass index (BMI) mediates the anti-inflammatory effect on PE.
• Findings support exploring anti-inflammatory therapies for VTE and warrant further investigation into IL-1β signaling, BMI, and PE.