Obesity is a complex phenotype characterized by general and regional excess of adipose tissue. It is a strong risk factor for increased morbidity and mortality and a major public health problem in the developed and developing world. Obesity has a substantial genetic component demonstrated in family studies and segregation analyses, but there is little consistency in the identification of major susceptibility loci for obesity. In this study the investigators propose to conduct a genome-wide scan for obesity susceptibility loci among adult Samoans of Polynesia. There is a high prevalence of obesity among Samoans, ranging from 80-90 percent among rapidly modernizing American Samoans to 40-60 percent among more traditional Western Samoans. Samoans have reduced genetic diversity due to their unique population history, and in combination with their rapid obesity responses to altered diet and activity patterns, we suspect they will have different obesity susceptibility loci than in other populations. The objectives of the study will be achieved through three specific aims. First, obesity phenotypes will be collected including fat mass and percent body fat, body mass index (BMI), fat distribution from circumferences and skin folds using anthropometry, and fasting serum leptin data, from 1,200 adults in approximately 60 extended pedigrees in American Samoa and 60 extended pedigrees in Western Samoa. Second, a genome-wide scan will be conducted using a panel of highly polymorphic genetic markers with average spacing of 10 cM between markers. Third, the location of obesity susceptibility loci will be determined by multipoint linkage analysis primarily based on the powerful and flexible variance components approach. Scientifically, Samoans offer a compelling opportunity to study the genetics of obesity in a population highly susceptible to obesity. The study has public health significance because it may identify obesity susceptibility loci applicable for general populations besides Samoans, as well as providing valuable information for the long-term effort to understand the etiology of Samoan obesity and develop interventions with high-risk individuals and families.
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