Sibling pair linkage and association studies between bone mineral density and the insulin-like growth factor I gene locus

A major determinant of the risk for osteoporosis in later life is bone mine ral density (BMD) attained during early adulthood. BMD is a complex trait t hat presumably is influenced by multiple genes. Insulin-like growth factor I (IGF-I) is an attractive candidate gene for osteoporosis susceptibility, because IGF-I has marked effects on bone cells and has been implicated in t he pathogenesis of osteoporosis. The IGF-I gene contains a microsatellite r epeat polymorphism approximately I kb upstream from the IGF-I gene transcri ption start site, and previous investigators have found a higher prevalence of the 192/192 genotype of this polymorphism among men with idiopathic ost eoporosis compared to controls. In this study we used this IGF-I polymorphi sm to test for an association between this polymorphism and EMD in our larg e population of premenopausal women (1 sister randomly chosen from 292 Cauc asian and 71 African-American families), We also used this polymorphism to detect linkage to BMD elsewhere in the IGF-I gene or in a nearby gene using sibling pair linkage analysis in healthy premenopausal sister pairs (542 s ibling pairs: 418 Caucasian and 124 African-American). Neither test provide d any evidence of linkage or association between the IGF-I gene locus and s pine or femoral neck BMD in Caucasians or African-Americans.