Evidence for a major gene influence on abdominal fat distribution: The Minnesota Breast Cancer Family Study

Abdominal fat has been shown to be an important risk factor fur many chroni c conditions, including diabetes, heart disease, and breast cancer. The obj ective of this study was to provide evidence for a major gene influence on the ratio of waist to hip circumference (WHR), a measurement commonly used in large scale studies to indicate the presence of abdominal fat. Segregati on analysis was conducted on three subsets of families from the Minnesota B reast Cancer Family Study. One analysis was conducted among families with W HR measurements on all women. Two additional analyses were conducted on sub sets of women stratified on menopausal status. Multiple regression analysis was used to identify factors associated with WHR expressed as a continuous trait. Complex segregation analyses were performed on the continuous trait of WHR and the covariates identified in the regression analysis. In the an alysis of all women, all hypotheses were rejected. Among premenopausal wome n, the environmental hypothesis with no heterogeneity between generations f it the data best (P = 0.85). However, among postmenopausal women, the requi rements for conclusion of the presence of a major gene were met. AH non-Men delian hypotheses were rejected (P < 0.0001), but the additive hypothesis w as not rejected (P = 0.19) and provided the best fit to the data. The putat ive major gene identified by this model accounted for 42% of total phenotyp ic variance in WHR among these postmenopausal women. The allele for high WH R had a frequency of 27%. These findings support the hypothesis that the di stribution of abdominal fat in postmenopausal women is under genetic contro l.