Federica Galimberti (Italy)
University of Milan - Epidemiology and Preventive Pharmacology Service (SEFAP) Department of Pharmacological and Biomolecular SciencesAuthor Of 1 Presentation
O016 - Mendelian randomization mediation analysis of the direct and indirect effects of adiposity on coronary artery disease (ID 1136)
Abstract
Background and Aims
Increased adiposity is associated with an increased risk of coronary artery disease (CAD). Whether adiposity has a direct causal effect on the risk of CAD, or whether the effect of adiposity on CAD is mediated indirectly through the effect of adiposity on other risk factors is unknown.
Methods
We constructed a body mass index (BMI) instrumental variable genetic score composed of 96 variants associated with BMI. We used this instrument to conduct a multivariable Mendelian randomization (MR) mediation analysis to estimate the direct and indirect effects of BMI on CAD. The study included individual level data on 445,774 participants including 23,032 cases of CAD and 28,563 cases of type II diabetes (T2D); and summary data on up to 877,643 participants including 63,746 cases of CAD and 26,676 cases of T2D.
Results
A one unit increase in BMI was associated with a 7% increased odds of CAD (OR:1.07; 95%CI:1.05-1.09, p=1.6E-10), a 25% increased odds of T2D (OR:1.25, 95%CI:1.23-1.28, p=2.2E-131); and 0.34 mmHg increase in systolic blood pressure (SBP) (95%CI:0.25-0.42, p=8.5E-15). A one unit increase in BMI was also associated with a 0.02 mmol/L increase in triglycerides (95%CI:0.02-0.03, p=4.9E-21), but not with increased apolipoprotein B levels. In MR mediation analyses, 80.0% of the effect of BMI on the risk of CAD was mediated through BMI induced increases in SBP (29.6%) and T2D risk (50.4%).
Conclusions
The vast majority of the effect of increased BMI on the risk of CAD appears to be mediated indirectly through the effect of BMI on SBP and T2D.
Presenter of 1 Presentation
O016 - Mendelian randomization mediation analysis of the direct and indirect effects of adiposity on coronary artery disease (ID 1136)
Abstract
Background and Aims
Increased adiposity is associated with an increased risk of coronary artery disease (CAD). Whether adiposity has a direct causal effect on the risk of CAD, or whether the effect of adiposity on CAD is mediated indirectly through the effect of adiposity on other risk factors is unknown.
Methods
We constructed a body mass index (BMI) instrumental variable genetic score composed of 96 variants associated with BMI. We used this instrument to conduct a multivariable Mendelian randomization (MR) mediation analysis to estimate the direct and indirect effects of BMI on CAD. The study included individual level data on 445,774 participants including 23,032 cases of CAD and 28,563 cases of type II diabetes (T2D); and summary data on up to 877,643 participants including 63,746 cases of CAD and 26,676 cases of T2D.
Results
A one unit increase in BMI was associated with a 7% increased odds of CAD (OR:1.07; 95%CI:1.05-1.09, p=1.6E-10), a 25% increased odds of T2D (OR:1.25, 95%CI:1.23-1.28, p=2.2E-131); and 0.34 mmHg increase in systolic blood pressure (SBP) (95%CI:0.25-0.42, p=8.5E-15). A one unit increase in BMI was also associated with a 0.02 mmol/L increase in triglycerides (95%CI:0.02-0.03, p=4.9E-21), but not with increased apolipoprotein B levels. In MR mediation analyses, 80.0% of the effect of BMI on the risk of CAD was mediated through BMI induced increases in SBP (29.6%) and T2D risk (50.4%).
Conclusions
The vast majority of the effect of increased BMI on the risk of CAD appears to be mediated indirectly through the effect of BMI on SBP and T2D.