A new look at the genetic and environmental coherence of metabolic syndrome components

Abstract

Objective Metabolic syndrome, a clustering of risk factors including insulin resistance, dyslipidemia, central obesity, and hypertension, increases risk for cardiovascular disease and cognitive decline. The etiology of the risk factors' cohesion remains unclear. How genetic and environmental influences explained co-occurrence of metabolic syndrome components was examined. Methods Continuous measures of body mass index (BMI), waist circumference, blood pressure (BP), fasting insulin and glucose, high-density lipoprotein cholesterol (HDL), and triglycerides from 1,193 middle-aged twin men participating in the Vietnam Era Twin Study of Aging at average age 62 (range 56-67) were analyzed using multivariate biometrical modeling. Results Four heritable factors were found: adiposity (BMI, waist circumference), insulin resistance (glucose, insulin), lipids (HDL, triglycerides), and BP (systolic, diastolic). Heritabilities were 0.42-0.68. In the best-fitting model, insulin resistance, lipids, and adiposity comprised a higher-order latent genetic factor. Adiposity and BP shared genetic influences independent of the latent genetic factor. All factors aggregated on a latent unique environmental factor. Conclusions Metabolic syndrome components form the equivalent of two genetic factors. BP was genetically unrelated to insulin resistance and lipids. Adiposity was the only characteristic genetically and environmentally related to all other factors. These results inform strategies for gene discovery and prediction of health outcomes.