Abstract
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.
Highlights
Epidemiological studies have estimated that the prevalence of overweight/obesity increased by approximately 41% between 1980 and 20131
We found a positive association of body mass index (BMI) with coronary artery disease (CAD) from the inverse-variance weighted (IVW) results (odds ratio (OR) 1.37, 95% CI 1.15–1.63)
The causal estimate from Mendelian randomization (MR)-Egger was 1.44, and the estimated effect size from the weighted median method was consistent with the IVW results (Table 1)
Summary
Epidemiological studies have estimated that the prevalence of overweight/obesity increased by approximately 41% between 1980 and 20131. Insulin resistance may increase cardiovascular risk through increased activity of the systemic renin-angiotensin system[9], subclinical inflammation (estimated by C-reactive protein)[10], and lower natriuretic peptide levels[11], all of which combine to further increase the likelihood of developing CAD12 Inconsistent findings from these observational studies reflect the limitations of observational studies, which cannot fully eliminate the influence of confounding factors and are susceptible to recall bias and reverse causation[13]. Two-sample MR analyses were performed to quantify and contrast causal estimates of the association of different obesity-related traits with CAD, including BMI, hip circumference (HC), WC, and WHR both with and without adjustment for BMI We hypothesized that this method could uncover causal relationships between obesity-related traits and CAD and extend the measures of adiposity and fat distribution as exposure proxies
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
