Association Between Waist Circumference and Coronary Artery Disease: Evidence from the NHANES 1999–2023 Cross-Sectional Data and Mendelian Randomization Analysis

Background: Central obesity, as indicated by waist circumference (WC), is a major risk factor for coronary artery disease (CAD). However, the independent causal role of WC in CAD remains underexplored, particularly after adjusting for metabolic comorbidities such as hypertension and diabetes. Objectives: This study aims to evaluate the causal relationship between WC and CAD using a two-pronged approach: propensity score-matched observational analysis and Mendelian randomization (MR) analysis. Methods: Data from the National Health and Nutrition Examination Survey (NHANES) 1999–2023 were used for cross-sectional analysis, while genetic instrumental variables associated with WC were sourced from genome-wide association studies (GWAS). We performed inverse variance weighted (IVW) MR analysis and sensitivity tests including MR-Egger and leave-one-out analysis. Results: Propensity score matching showed that WC was significantly higher in the CAD group compared to controls (p < 0.001). MR analysis confirmed a causal relationship between increased WC and CAD risk, with an estimated causal effect size of 0.02884 (95% CI: 0.016, 0.041; p = 0.00000883). Sensitivity analyses validated the robustness of these findings. Conclusion: Our results provide strong genetic and observational evidence linking increased WC with a higher risk of CAD. These findings highlight the need for targeted interventions to reduce central obesity and prevent CAD, especially in populations prone to metabolic disorders.