The proposed analyses will examine specific genetic factors (single gene effects) in the familial transmission of obesity. Human obesity is a highly familial disorder which has been shown to be under substantial genetic control. The precise mode of genetic inheritance is unknown, and there may be more than one form of genetic obesity. A better understanding of the specific genetic causes of human obesity will contribute to the identification of more specific methods of treatment and prevention of this disorder. Genetic analyses will be conducted of weight and body mass index data on families from the Princeton School District Family Study of hyperlipidemia collected by the University of Cincinnati Lipid Research Clinic (LRC). These are carefully collected data on height and weight from 389 families. The main focus of the LRC research has been on the genetics of serum lipid levels, and the data on height and weight (from which indices of fatness will be constructed) have not been previously analyzed in this way. The proposed research will focus on the detection of single gene effects (through segregation analysis). The proposed genetic study is unique in that it will focus on obesity rather than on the whole range of human fatness (from fat to lean). Subdividing this large sample on the basis of extent of obesity and concomitant obesity and hyperlipidemia in the index case, the family member who led to the family's inclusion in the study, will make it possible to conduct tests of genetic heterogeneity. That is extreme obesity is highly familialand may be influenced more strongly by genetic factors than less extreme levels of fatness. Similarly, obesity is more common in families of obese patients who are also hyperlipidemic and thus concomitant obesity and hyperlipidemia by serve as a useful marker for one form of genetic obesity. Besides supporting this particular research project, the requested funding will aid a new investigator in developing an independent research program on the genetics of human obesity. The information gained from this study will lay the ground work for a larger prospective genetic family study of human obesity.
