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

OBJECTIVE: To test the hypothesis that obesity is causally associated with deep venous thrombosis (DVT). DESIGN: A Mendelian randomization design. SETTING: The Copenhagen General Population Study and the Copenhagen City Heart Study combined. SUBJECTS: Body mass index (BMI) measurements were available for 87, 574 individuals of Danish descent from the adult general population. All subjects completed questionnaires and were genotyped for the FTO rs9939609 variant. MAIN OUTCOME MEASURE: First events of DVT with or without pulmonary embolism (PE). ANALYSIS: The results were assessed using Cox regression, instrumental variable analysis and Poisson regression. RESULTS: Observationally, the risk of DVT increased with increasing BMI (P-trend 60 years and homozygous for Factor V Leiden) was 35% in obese individuals and 18% in normal-weight individuals. CONCLUSION: A strong observational association between obesity and DVT with or without PE, supported by a direct genetic association between the obesity-specific locus FTO and DVT with PE, implies that obesity is likely to be causally associated with DVT.