Populations of African ancestry have greater bone strength and lower osteoporotic fracture risk than other ethnic groups. Although genetic factors are recognized as the major determinants of bone strength and osteoporosis risk, surprisingly little is known about the genetic determinants of skeletal health in African populations. We are proposing a comprehensive genetic epidemiologic study of the bone strength phenotype within extended families of African origin. Its long-term goals are to detect, map and characterize genes influencing variation in bone related traits in a unique Afro-Caribbean population that has remarkably high bone mass. The proposed pilot project is the first-step towards achieving these long-term objectives. For this pilot project, we will recruit 250 individuals belonging to extended families of African ancestry. Families will be identified and recruited through the 40+ year old participants (probands) in our population-based Tobago Bone Health Study. All first-, second- and third-degree relatives of the proband and the proband's spouse who are aged 20+ years will be recruited. Information on family relationships, medical history, medication use, and environmental risk factors such as diet, smoking, alcohol use, and physical activity will be obtained from each family member. Family members will also undergo a comprehensive musculoskeletal evaluation including: measures of bone mass at several skeletal sites; femoral structural geometry; anthropometry; appendicular skeletal muscle mass; and muscle strength. Quantitative genetic methods will be used to estimate heritabilities, the effects of environmental covariates for each phenotype, and genetic correlations among phenotypes. Finally, we will create a biological specimen repository for future genetic studies (i.e., genome-wide linkage and family-based association analyses), and for subsequent proposals to measure biochemical indices of bone modeling/remodeling, markers of mineral metabolism, and growth factors. This pilot project will provide essential preliminary data to support a largerscale proposal to enroll additional families, conduct genome-wide linkage analyses to detect and map genes influencing bone related phenotypes, and investigate possible gene- gene and gene-environment interactions in families of African ancestry. The identification of these genes will likely yield fundamental insight on bone biology and may lead to the development of novel approaches to the diagnosis, treatment, and prevention of osteoporosis.
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