Evidence of a major gene with pleiotropic action for a cardiovascular disease risk syndrome in children younger than 14 years

D. B. Allison, S. Heshka and S. B. Heymsfield
Obesity Research Center, St Luke's/Roosevelt Hospital Center, Columbia University College of Physicians and Surgeons, New York, NY.

OBJECTIVE--To test the plausibility of the existence of a genetically based syndrome involving obesity, hypertension, and a central deposition of body fat. DESIGN--Survey of a random stratified sample of the US population. PARTICIPANTS--Male and female children aged 13 years or younger (mean, 5.3 years; SD, 3.7 years; median, 4.0 years; range, 6 months to 13 years) were chosen from National Health and Nutrition Examination Survey II data. INTERVENTIONS--None. MEASUREMENTS/MAIN RESULTS--Using multivariate commingling analysis, we evaluated the hypothesis that a major gene produces a syndrome involving the phenotypic indicators of body mass index (in kilograms per square meter), subscapular-to-triceps skinfold thickness ratio, systolic blood pressure, and diastolic blood pressure. Maximum likelihood estimation was used to test competing models. A model with three component distributions and unequal variance-covariance matrices fit significantly better than any competing model. CONCLUSIONS--Our findings support the existence of a distinct cardiovascular disease risk syndrome in children and suggest that it may be the result of a major gene with pleiotropic effects.