Associations of Triglyceride Glucose Index-related Obesity Indices, Genetic Susceptibility, and the Risk of Venous Thromboembolism: Insights from a Prospective Cohort Study

Abstract The triglyceride glucose (TyG) index and related obesity metrics are commonly recognized as important indicators of insulin resistance. However, the associations of several novel TyG-related obesity indices developed with venous thromboembolism (VTE) risk and their interactions with genetic susceptibility remain unclear. Cox proportional hazards models were applied to evaluate the associations between TyG-related obesity indices and VTE risk. Restricted cubic spline analyses were conducted to examine the linear and nonlinear relationships. Kaplan-Meier curves were performed to assess the cumulative risk of VTE. The additive interactions were assessed using the relative excess risk due to interaction, attributable proportion due to interaction. Discriminative performance was assessed using receiver operating characteristic curves. Participants in the highest quartiles of TyG, TyG-BMI, TyG-WC, TyG-WHtR, TyG-BRI, TyG-ABSI, TyG-WWI, and TyG-VAI exhibited elevated risk of VTE, with HRs (95% CIs) of 1.11 (1.04–1.17), 1.86 (1.76–1.98), 2.08 (1.94–2.22), 1.78 (1.67–1.89), 1.80 (1.70–1.92), 1.24 (1.17–1.33), 1.37 (1.29–1.46), and 1.19 (1.12–1.25), respectively. Individuals in the highest quartiles of TyG-related obesity indices had a higher cumulative incidence of VTE. ROC analysis indicated that TyG-WC and TyG-BRI showed comparatively better discriminative performance for VTE risk compared with other TyG-related obesity indices. Participants with both high genetic risk and high TyG-related obesity indices showed an increased risk of VTE. Higher TyG-related obesity indices were associated with an increased risk of VTE. Individuals with both higher quartiles of TyG-related obesity indices and high genetic susceptibility exhibited the highest VTE risk. Additive interactions were observed between TyG-related obesity indices and high genetic risk.