Inheritance of the waist-to-hip ratio in the National Heart, Lung, and Blood Institute Family Heart Study

Objective: Considering that waist-to-hip ratio (WHR) is a simple anthropome tric measure of obesity and is a better predictor of coronary heart disease than body mass index (BMI), the genetic underpinnings of WHR are of intere st. The inheritance pattern of WHR, before and after adjustment for BMI (WH R-BMI), was investigated in 2713 individuals from 1038 nuclear families in the National Heart, Lung, and Blood Institute Family Heart Study (NHLBI-FHS ). Research Methods and Procedures: Waist and hip measurements were taken twic e, and the means of the measurements were used to calculate the: WHR. Adjus tments for age were carried out separately by;ex, using stepwise multiple r egression procedures for WHR and WHR-BMI phenotypes. Segregation analysis w as applied using the unified model as implemented in the computer program P OINTER. Results: For age-adjusted WHR, the segregation results suggested an additiv e major gene that accounts for 35% of the phenotypic variance, and approxim ately 30% of the sample are homozygous for the "high" genotype, The results for age- and BMI-adjusted WHR were also compatible with a major gene; howe ver, die multifactorial model provided the most parsimonious fit to the dat a. Discussion: Although the genetic mechanisms for several obesity traits have been studied, tests of Mendelian segregation on this simple anthropometric measure (WHR) have not been reported previously, This study provides evide nce for the presence of a major gene for age-adjusted WHR, suggesting that it is an appropriate trait for further genetic analysis, especially because it has strong predictive value and probably relates biologically to cardio vascular risk.