Genetic Predisposition of Both Waist Circumference and Hip Circumference Increased the Risk of Venous Thromboembolism

Background Obesity, especially abdominal obesity, is an independent indicator of increased cardiovascular risk. Observational studies have shown an observational association between obesity and venous thromboembolism (VTE). As a type of VTE, pulmonary embolism (PE) is also associated with obesity. However, it is unclear whether the observed associations are causal or caused by confounding bias or reverse causality.Methods We performed a two-sample test by obtaining the exposure dataset of waist circumference (WC) and hip circumference (HC) from the Neale Laboratory Consortium's genome-wide association study summary data and the summary-level outcome data of VTE and PE from FinnGen Biobank of European ancestry to determine the causal effect of WC and HC on VTE and PE.Results All three Mendelian randomization methods displayed a positive association between WC/HC and VTE/PE. WC and HC were positively associated with VTE (odds ratio [OR] =1.803 per 1 standard deviation [SD] increase in WC, 95% confidence interval [CI] = 1.393-2.333; p < 0.001; OR = 1.479 per 1 SD increase in HC, 95% CI = 1.219-1.796; p < 0.001, respectively). Furthermore, we found a causal association between genetically predicted WC/HC and a higher risk of PE (OR = 1.929 per 1 SD increase in WC, 95% CI = 1.339-2.778, p < 0.001; OR = 1.431 per 1 SD increase in HC, 95% CI =1.095-1.869; p = 0.009, respectively). Conclusion There is a significant causal relationship between WC/HC and VTE/PE, which is consistent with observational studies. Taking measures to reduce WC/HC of obesity may help reduce the incidence of VTE/PE.

Automated summary

Obesity, especially abdominal obesity, is associated with an increased risk of venous thromboembolism and pulmonary embolism. This study used genetic data and summary-level epidemiological data to demonstrate a causal relationship between waist circumference/hip circumference and the risk of VTE and PE. Measures to reduce obesity may help decrease the incidence of VTE and PE.