Heritability of Multivariate Factors of the Metabolic Syndrome in Nondiabetic Japanese Americans

Abstract

A rapidly growing body of evidence demonstrates important associations between the metabolic syndrome, characterized by a cluster of risk factors or phenotypes that include dyslipidemia, central obesity, hypertension, and hyperinsulinemia, and both cardiovascular disease and type 2 diabetes. The purpose of the present study was to characterize the metabolic syndrome in a sample of 432 individuals from 68 Japanese-American families, using factor analysis of quantitative phenotypes, and to estimate the heritability of these independent factors. Using nine characteristic phenotypes that included LDL particle size and C-reactive protein (CRP), factor analysis identified three multivariate factors interpreted as lipids, body fat/insulin/glucose/CRP, and blood pressure, explaining 65% of the variance. Heritability analysis revealed significant genetic effects on all of the factors: lipids (h2 = 0.52, P < 0.001), body fat/insulin/glucose/CRP (h2 = 0.27, P = 0.016), and blood pressure (h2 = 0.25, P = 0.026). This analysis shows that independent, multivariate factors of the metabolic syndrome are heritable, demonstrating genetic influences on the underlying pathophysiological mechanisms of the syndrome.