LINKAGE OF A QTL CONTRIBUTING TO NORMAL VARIATION IN BONE-MINERAL DENSITY TO CHROMOSOME 11Q12-13

Osteoporosis is a leading public health problem that is; responsible f or substantial morbidity and mortality. A major determinant of the ris k for osteoporosis in later life is bone mineral density (BMD) attaine d during early adulthood. BMD is a complex trait that presumably is in fluenced by multiple genes. Recent linkage of three Mendelian BMD-rela ted phenotypes, autosomal dominant high bone mass, autosomal recessive osteoporosis-pseudoglioma, and autosomal recessive osteopetrosis to c hromosome 11q12-13 led us to evaluate this region to determine if the underlying gene(s) could also contribute to variation in BMD in the no rmal population. We performed a linkage study in a sample of 835 preme nopausal Caucasian and African-American sisters to identify genes unde rlying BMD variation. A maximum multipoint LOD score of 3.50 with femo ral neck BMD was obtained near the marker D11S987, in the same chromos omal region as the three Mendelian traits mentioned above. Our results suggest that the gene(s) underlying these Mendelian phenotypes also p lay a role in determining peak BMD in the normal population and are th e first using linkage methods to establish a chromosomal location for a gene important in determining peak BMD. These findings support the h ypothesis that a gene responsible for one or more of the rare Mendelia n BMD traits linked to chromosome 11q12-13 has an important role in os teoporosis in the general population.