This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is a continuation of a previous study (San Antonio Family Osteoporosis Study, or SAFOS) which enrolled 897 individuals from 34 families from 1997-2001, in conjunction with the San Antonio Family Heart Study (SAFHS). From the results of the SAFOS study, strong evidence was detected for linkage of forearm bone mineral density (BMD) to a region on chromosome 4p (multipoint lod score = 4.8). Associations were also observed between increased BMD with both diabetes and serum insulin levels, although this latter correlation as not independent of obesity. Also observed was a strong positive correlation between carotid wall thickening, a subclinical measure of atherosclerosis, and BMD in women ages 40 years and older, although in men a significant correlation was also detected but in the opposite direction. This study seeks to enroll 950 subjects already enrolled in the SAFHS who will be returning for their 10-year visit. Most will have also been enrolled in the first SAFOS study, which included measurement of bone mineral density. BMD will be re-measured to enable investigators to determine whether there has been a change in BMD over five years. It is hypothesized that serum insulin levels will be positively correlated with five-year change in BMD, and that oxidized LDL concentrations will be a common risk factor predisposing subjects to both osteoporosis and subclinical atherosclerosis. A genome scan of five-year changes will be performed, and it is anticipated that multiple linkages to this trait will be identified, some of which will overlap with loci previously shown to be linked to the baseline measure of BMD, and others not previously identified as being linked to BMD. Molecular studies will be initiated, with the goal of fine-mapping the QTL on chromosome 4 identified as being linked to BMD. To begin this effort, investigators will identify and genotype SNPs within positional candidate genes that map to the linked region and will perform association analyses to detect whether linkage disequilibrium over the previous five years are associated with hyperinsulinemia or cardiovascular risk factors. They will also perform genetic studies, including determining whether any quantitative trait loci influence the rate of change of bone mineral density.
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