African Americans experience a higher prevalence of obesity than do whites, particularly among women. Recent advances in genetics have made it possible to identify the molecular determinants of obesity. Based on an on-going international collaborative family study, the investigators propose to recruit a community sample of black families in Chicago and Nigeria. In Chicago they will recruit 400 families with 4 or more first degree members (1,600 individuals). In Nigeria, they will also identify a sample of 400 families with 4 or more members (1,600). During a clinical exam they will measure height, weight, fat mass, percent body fat, fat free mass, resting metabolic rate, and waist and hip circumference. Blood will be drawn for assays of glucose, insulin and leptin and genomic DNA will be extracted. Using the candidate gene approach they will examine the potential roll of known genetic markers for obesity. As of this writing, the priority list for candidates includes: a quantitative train locus (QTL) on chromosome 7 (ob gene locus), QTL on chromosome 2, pro-opiomelanocortin, beta3 adrenergic receptor, thyroid hormone receptor genes (TR alpha and TR beta); Uncoupling protein-2 and -3, melanocortin-4 receptor. The high priority loci may change to accommodate new findings. Statistical analyses of the sampled families will first be carried out using path and segregation analysis. Genotyping will be completed on all family members and both association and linkage analysis conducted. The contrast of these families, drawn from populations with similar genetic background living in different social environments, will make it possible to assess the relative impact of environmental conditions on the familiality of obesity traits. In addition, physiologic processes which relate to obesity, like leptin, can be examined in these high and low risk population groups. Estimation of allele frequencies in the Nigerian sample will make it possible to estimate the potential role of admixture in US blacks and help guide efforts to identify specific makers or haplotypes associated with risk in this population. The investigators state that an urgent need exists to undertake large scale family studies among US blacks to identify genetic factors which condition risk of obesity. They further state that the present study will also have sufficient power to permit a genome scan, which is planned in the second stage. Comparison to the genetically related sample in West Africa will provide an environmental contrast and help clarify the impact of European admixture at the loci of interest.
