Childhood obesity is predictive of adult obesity and the degree of ponderosity (as measured by body weight relative to height) in adults has been shown to be an important predictor of morbidity as well as mortality from atherosclerotic cardiovascular disease. We conducted a family study in Muscatine, Iowa of 1,580 individuals in 284 families to evaluate the genetic contribution to familial clustering of levels of the body mass index (BMI=kg/m2) and found evidence that the segregation of two alleles (designated as L for lower and H for higher BMI) at a recessive locus explains 35%, while polygenic loci explain 42% of the variability in BMI in this population. We estimate that 37% of the individuals in this population are carriers of the H gene and that 6% have the HH genotype. Several rodent models of recessive obesity have also been identified and the traits have been mapped to rodent chromosomal regions which are syntenic with regions on human chromosomes 1 and 7. These results suggest that a search for human genes that are responsible for the observed variability in BMI is now an important venture. In the proposed study, we will focus on three questions: 1) Are there human genes or DNA sequences which have measurable effects on quantitative indices of obesity or on quantitative traits that are associated with obesity among school-age siblings from Muscatine, Iowa ? 2) What effects do the genotypes at linked loci have on quantitative indices of obesity and on quantitative traits that are associated with obesity in nuclear families from Muscatine? 3) Is there evidence for linkage of BMI to candidate loci identified from the sib-pair analyses in families who appear to be segregating the H gene? This study should add to our understanding of the genetic factors involved in the determination of obesity and may lead to early identification of individuals and families at high risk for the chronic diseases that are associated with obesity.
