Genetic Association of Waist-to-Hip Ratio With Diabetes and CHD

Study Questions:

Is there a causal relationship between waist-to-hip ratio (WHR) and coronary heart disease (CHD)?


Based on previous genome-wide association studies (GWAS), a genetic risk score for WHR adjusted for body mass index (BMI) was developed to determine associations with cardiometabolic traits, type 2 diabetes mellitus (DM), and CHD. This mendelian randomization analysis combined case-control and cross-sectional data sets from four GWAS including 322,154 participants, as well as individual-level, cross-sectional data including 111,986 individuals. Estimates for DM and CHD were derived from summary statistics of two separate GWAS including 149,821 and 184,305 individuals, respectively, combined with individual-level data from the UK Biobank.


A 1-standard deviation (SD) increase in WHR adjusted for BMI mediated by the polygenic risk score was associated with 27 mg/dl higher triglyceride levels, 4.1 mg/dl higher 2-hour glucose levels, and 2.1 mm Hg higher systolic blood pressure (each p < 0.001). A 1-SD genetic increase in WHR was also associated with a higher risk of type 2 diabetes (odds ratio, 1.77) and CHD (odds ratio, 1.46).


The authors concluded that a genetic predisposition to higher WHR was associated with increased risk of type 2 DM and CHD.


Elevated WHR has been associated with atherosclerosis severity and myocardial infarction in several studies, although the degree to which elevated WHR directly influences CHD is unknown. Mendelian randomization studies have proven useful to infer causal relationships between diseases and biomarkers when genetic contributions for the biomarker variance have been identified. This study provides support for a direct relationship between elevated WHR and CHD, and suggests that therapeutic targeting of pathways that influence distribution of body fat may reduce risk for DM and CHD.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Atherosclerotic Disease (CAD/PAD), Hypertriglyceridemia, Lipid Metabolism

Keywords: Atherosclerosis, Biological Markers, Blood Pressure, Body Mass Index, Coronary Artery Disease, Diabetes Mellitus, Type 2, Dyslipidemias, Genetic Predisposition to Disease, Genome-Wide Association Study, Glucose, Metabolic Syndrome X, Primary Prevention, Risk Factors, Triglycerides, Waist-Hip Ratio

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