Age-related osteoporotic fractures result from an increase in bone fragility due to a reduction in bone strength with aging in combination with increased propensity to fall.. Several highly heritable phenotypes contribute to bone strength, including bone mineral density (BMD), bone structure, and bone quality. Successful localization and identification of genes underlying the components of bone strength, and in turn osteoporosis, depend upon accurate phenotypic measurement and optimal genetic analyses. During the tenure of the current award, members of this Core have worked with the Program Project Grant investigators to successfully identify several chromosomal regions that contain genes influencing peak bone strength in white and black men and women, as well as in rats. The goal of this renewal application is to further define QTLs linked to phenotypes of peak bone strength, identify sex-specific QTLs , and identify the genes that underlie bone fragility. To accomplish these goals, this Core will: 1) modify and adapt the study designs of the three projects, as necessary, to exploit novel methodological advances in genetic analyses; 2) perform linkage and association analyses to identify genes contributing to bone strength; and 3) develop bioinformatics resources to assist in the identification of the genes contributing to bone strength.
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