Effect of visceral adipose tissue mass on coronary artery disease and heart failure: A Mendelian randomization study

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Abstract
Objectives Obesity is associated with coronary artery disease (CAD) and its risk factors in observational studies. This two-sample Mendelian randomization (MR) study investigated the effect of visceral adipose tissue (VAT) mass on coronary artery disease (CAD), myocardial infarction (MI) and heart failure (HF). Methods Genetic variants (220 SNPs, P < 5 × 10−8) associated with VAT mass were obtained from a genome-wide association study (GWAS) in the UK Biobank. Genetic associations with CAD outcomes including CAD and myocardial infarction (MI) were obtained from the CARDIoGRAMplusC4D 1000 Genomes-based GWAS (including up to 60,801 cases and 123,504 controls) and data on patients with HF were obtained from the HERMES Consortium (47,309 cases and 930,014 controls). The effects of VAT mass on CAD outcomes and HF were estimated using the inverse variance weighted (IVW) method. Sensitivity analysis and multi-variable MR were used to examine the stability of the IVW results. Results Our results showed that genetically predicted higher VAT mass was associated with increased risk of CAD (odds ratio [OR] 1.57, 95% confidence interval [CI], 1.44–1.71; P = 7.62 × 10−24), MI (OR 1.63, 95% CI: 1.48–1.79; P = 3.76 × 10−24) and HF (OR 1.71, 95% CI: 1.60–1.83; P = 1.72 × 10−53). These findings remained significant in the sensitivity analysis and multi-variable MR. Conclusion This MR study suggests that genetic determinants of VAT mass are causally associated with CAD, MI and HF.

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