This is a Shannon Award providing partial support for the research projects that fall short of the assigned institute's funding range but are in the margin of excellence. The Shannon Award is intended to provide support to test the feasibility of the approach; develop further tests and refine research techniques; perform secondary analysis of available data sets; or conduct discrete projects that can demonstrate the PI's research capabilities or lend additional weight to an already meritorious application. The abstract below is taken from the original document submitted by the principal investigator. Osteoporosis is a common condition characterized by low bone mineral density and decreased bone strength, which leads to a greater susceptibility to fractures. Although epidemiologic studies indicate that osteoporosis is a multifactorial trait with a large hereditary component, little is know about the role of single genes in its pathogenesis. The candidate gene approach will be used in association studies to identify genes which are important in determining bone mineral density. Genetic variation in six genes will be analyzed in 2083 women from three well-characterized longitudinal studies of bone mineral density. The genes for the vitamin D receptor, osteocalcin, osteonectin, osteopontin, and COL1A1 and COL1A2, the genes which encode the protein chains of type I procollagen, were selected for study because of the relative abundance of their protein products in bone, their potential role in bone formation, and in some cases, because of preliminary studies which implicate them as candidate genes for osteoporosis. Mutational analysis will be performed on genes for which an association with bone mineral density is identified. The effect of selected modifiers of bone mineral density will be studied in the context of genotype. Identification of genes which determine bone mineral density has the potential to provide insight into the biologic nature of the variation which underlies different susceptibilities to osteoporosis, and their interaction with known environmental modifiers.