Assessing causal estimates of the association of obesity-related traits with coronary artery disease using a Mendelian randomization approach

Obesity-related traits have been associated with coronary artery disease (CAD) in observational studies, but these associations may be biased by confounding factors and reverse causation. In this study, we specifically conducted two-sample Mendelian randomization (MR) analyses to overcome these limitations and test the associations of obesity-related traits (other than body mass index (BMI)) (n = 322,154) with CAD (22,233 cases and 64,762 controls) by using summary-level data from previous studies. The methods utilized to estimate these associations included the inverse-variance weighted method, the weighted median method and MR-Egger regression. Our results supported causal effects of BMI, hip circumference (HC), waist circumference (WC), and waist-hip ratio (WHR) on CAD. The associations of BMI-adjusted HC and WC with CAD were reversed, unlike that of WHR. In MR analyses excluding overlapping single nucleotide polymorphisms (SNPs) from obesity-related traits, the associations of these traits with CAD were preserved. The associations of BMI-adjusted HC and WC with CAD require further investigation, as collider stratification may be occurring. Additionally, central adiposity (measured by WHR) separated from general adiposity (measured by BMI) and general adiposity might pose similar risks for CAD. In clinical practice, physicians should pay attention to the potential effects of different obesity-related traits on CAD.