Childhood obesity is associated with a constellation of metabolic derangements including glucose intolerance, hypertension, and dyslipidemia, referred to as metabolic syndrome. The purpose of this study was to investigate genetic and environmental factors contributing to the metabolic syndrome in Hispanic children. Metabolic syndrome, defined as having three or more metabolic risk components, was determined in 1030 Hispanic children, ages 4 -19 y, from 319 families enrolled in the VIVA LA FAMILIA study. Anthropometry, body composition by dual energy x-ray absorptiometry, clinical signs, and serum biochemistries were measured using standard techniques. Risk factor analysis and quantitative genetic analysis were performed. Of the overweight children, 20%, or 28% if abnormal liver function is included in the definition, presented with the metabolic syndrome. Odds ratios for the metabolic syndrome were significantly increased by body mass index z-score and fasting serum insulin; independent effects of sex, age, puberty, and body composition were not seen. Heritabilities Ϯ SE for waist circumference, triglycerides (TG), HDL, systolic blood pressure (SBP), glucose, and alanine aminotransferase (ALT) were highly significant. Pleiotropy (a common set of genes affecting two traits) detected between SBP and waist circumference, SBP and glucose, HDL and waist circumference, ALT and waist circumference, and TG and ALT may underlie the clustering of the components of the metabolic syndrome. Significant heritabilities and pleiotropy seen for the components of the metabolic syndrome indicate a strong genetic contribution to the metabolic syndrome in overweight Hispanic children. Childhood obesity in the United States has steadily increased in the past two decades according to NHANES, especially among Hispanic children (1,2). The prevalence of overweight, defined as Ն95th BMI percentile, was Ͼ20% among Mexican-American children. Childhood obesity is associated with several metabolic and endocrine derangements including glucose intolerance, hypertension, and dyslipidemia that predispose to early development of CVD and T2D (3). This constellation of metabolic derangements has been defined in adults as the metabolic syndrome. According to the National Cholesterol Education Program (NCEP) Adults Treatment Plan (ATP) III, the metabolic syndrome is defined as having three or more of the following risk factors: abdominal obesity, raised TG, low HDL cholesterol, elevated blood pressure, or glucose intolerance (4). Although abnormal liver function is not conventionally considered among the constellation of risk factors for the metabolic syndrome, it most likely shares common molecular pathway(s) and may contribute independently to the pathophysiology of CVD and T2D and lead to fatty liver disease (5). Abnormal liver function thus may be considered as part of the constellation of metabolic derangements, even in children. In severely obese adults, the metabolic syndrome was strongly correlated with steatosis, fibrosis, and cirrhosis of th...