Obesity as a causal risk factor for deep venous thrombosis: a Mendelian randomization study

Area of Science:

• Genetics and Epidemiology
• Cardiovascular Health
• Obesity Research

Background:

• Deep venous thrombosis (DVT) is a significant health concern.
• The relationship between obesity and DVT requires further causal investigation.
• Obesity is a growing global health issue with numerous comorbidities.

Purpose of the Study:

• To investigate the causal association between obesity and deep venous thrombosis (DVT).
• To utilize Mendelian randomization to explore genetic links between body mass index (BMI) and DVT risk.
• To assess the impact of obesity on DVT, with and without pulmonary embolism (PE).

Main Methods:

• Employed a Mendelian randomization design using data from the Copenhagen General Population Study and Copenhagen City Heart Study.
• Included 87,574 individuals of Danish descent, measuring body mass index (BMI) and genotyping the FTO rs9939609 variant.
• Analyzed data using Cox regression, instrumental variable analysis, and Poisson regression for first-time DVT events.

Main Results:

• A strong observational link was found between increased BMI and elevated DVT risk (P-trend < 0.0001).
• Hazard ratios for DVT increased with BMI levels, and significantly for DVT with PE.
• The FTO genotype associated with higher BMI showed a trend towards increased DVT risk, particularly for DVT with PE. Instrumental variable analysis indicated a causal odds ratio of 1.86 (95% CI 1.14-3.02) for DVT complicated by PE per 1 kg m(-2) increase in BMI.

Conclusions:

• The study provides strong evidence supporting a causal relationship between obesity and deep venous thrombosis (DVT).
• Genetic data, specifically the FTO locus, reinforces the link between obesity and DVT, including cases with pulmonary embolism (PE).
• Obesity is identified as a likely causal factor for DVT, highlighting the importance of weight management in preventing thrombotic events.