Physicians' Academy for Cardiovascular Education

Causal relationship of central and general adiposity with CHD and T2DM

Causal Associations of Adiposity and Body Fat Distribution with Coronary Heart Disease, Stroke Subtypes and Type 2 Diabetes: A Mendelian Randomization Analysis

Dale C, Fatemifar G, Palmer P, et al; on behalf of UCLEB consortium and METASTROKE consortium - Circulation. 2017; published online ahead of print


Many observational studies evaluating the associations between adiposity and the risk of coronary heart disease (CHD), stroke and type 2 diabetes mellitus (T2DM), report consistent results with different measures of adiposity [1,2]. Some studies found a stronger association between the waist-hip-ratio (WHR) and myocardial infraction (MI) or stroke compared with BMI, whereas others found that the waist circumference (WC) is independently associated with CHD [3-5]. Based on observational studies it is difficult to understand the implications of different adiposity measures on cardiovascular disease (CVD) risk estimation because [6]:

Mendelian randomization (MR) studies minimise the bias resulting from confounding, regression dilution bias and reverse causation, but they are susceptible to bias from pleiotropy, e.g. the association of genetic variants with more than one variable.

In this study, MR analyses of BMI and WHR are performed with recently developed methods that are robust to pleiotropy, to quantify and contrast causal associations of central and general adiposity with cardiometabolic disease, using data from 14 studies and 4 consortia; this included 66 842 CHD cases, 12 389 ischemic stroke (IS) cases and 34 840 T2DM cases.

Main results


In a Mendelian randomization analysis of 14 studies and 4 consortia, there was a causal relationship of both central and general adiposity with the risk of CHD and T2DM. Central adiposity was associated with the risk of IS and may represent a higher risk for stroke and CHD. These results suggest that different types of adiposity may have different effects on CVD risk.


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Find this article online at Circulation