Genetic and environmental influences on factors associated with cardiovascular disease and the metabolic syndrome

Abstract

The relative influence of genetics and the environment on factors associated with cardiovascular disease (CVD) and metabolic syndrome (MetS) remains unclear. We performed model-fitting analyses to quantify genetic, common environmental, and unique environmental variance components of factors associated with CVD and MetS [waist circumference, blood pressure, fasting plasma glucose and insulin, homeostatic model assessment of insulin resistance (HOMA-IR), and fasting plasma lipids] in adult male and female monozygotic twins reared apart or together. We also investigated whether MetS components share common influences. Plasma cholesterol and triglyceride concentrations were highly heritable (56-77%, statistically significant). Waist circumference, plasma glucose and insulin, HOMA-IR, and blood pressure were moderately heritable (43-57%, statistically significant). Unique environmental factors contributed to the variance of all variables (20-38%, perforce statistically significant). Common environmental factors contributed 23, 30, and 42% (statistically significant) of the variance of waist circumference, systolic blood pressure, and plasma glucose, respectively. Two shared factors influenced MetS components; one influenced all components except HDL cholesterol, another influenced only lipid (triglyceride and HDL cholesterol) concentrations. These results suggest that genetic variance has a dominant influence on total variance of factors associated with CVD and MetS and support the proposal of one or more underlying pathologies of MetS.

Fig. 1.

Path diagram of the univariate MZA/MZT GCE twin model. C, common environmental factors; E, unique environmental factors; G, genetic factors; MZA, monozygotic twins reared apart; MZT, monozygotic twins reared together; P₁, phenotype of twin 1; P₂, phenotype of twin 2; g, c, e are path coefficients. Circles represent latent (unmeasured) variables. Squares represent observed (measured) variables. Single-headed arrows represent hypothesized casual relationships between variables. Double-headed arrows represent correlation or covariance between variables.

Fig. 2.

Variance components from univariate GCE model for components of cardiometabolic syndrome. C, common environmental; DBP, diastolic blood pressure; E, unique environmental; FG, fasting plasma glucose; FI, fasting plasma insulin; G, genetic; HDL, fasting plasma HDL; HOMA-IR, homeostatic model assessment of insulin resistance; LDL, fasting plasma LDL; SBP, systolic blood pressure; TC, fasting plasma total cholesterol; TG, fasting plasma triglycerides; VLDL, fasting plasma VLDL; WC, waist circumference. ^a The variable was transformed by a Blom transformation. ^b Significant C component. All variables have significant G and E components. ^c The variable was transformed by multiplying the natural log of the variable by 100.

Fig. 3.

Hypothesis-driven two-factor common pathway model path diagram of the metabolic syndrome. Rectangles represent observed variables. Circles represent latent or unmeasured variables. Single-headed arrows represent hypothesized casual relationships between variables. Double-headed arrows represent variance. Path coefficients are standardized parameter estimates and 95% confidence intervals are reported in parentheses. Darkened lines indicate significant paths. Subscripts indicate variable or factor under influence. C, common environmental factors; DBP, diastolic blood pressure; E, unique environmental factors; FG, transformed (100 × ln of) fasting plasma glucose; G, genetic factors; HDL, fasting plasma HDL cholesterol; TG, transformed (100 × ln of) fasting plasma triglycerides; WC, Blom transformation of waist circumference.