BETHESDA, MD. — New chromosomal regions that possibly contain genes controlling bone quality were recently identified in the first genome-wide linkage scan of cross-sectional bone geometry in humans.
The few reported genetic studies of cross-sectional geometry have shown that the heritability is greater than 50%, “which means that in the general population, more than 50% of the phenotypic variation can be attributable to genetic events,” Hui Shen said at a meeting on bone quality.
In a prospective study of 79 white pedigrees composed of 1,816 individuals, Mr. Shen of Creighton University, Omaha, Neb., and his colleagues calculated logarithmic odds (LOD) scores for bone geometry parameters at the femoral neck, including cross-sectional area, cortical thickness, endocortical diameter, sectional modulus, and buckling ratio in relation to 451 microsatellite markers.
On chromosome 10q26, the researchers calculated an LOD score of 3.29, the highest recorded in the study, for the buckling ratio at the femoral neck. This indicates that the odds are nearly 2,000 to 1 in favor of genetic linkage between the two loci.
Three bone geometry parameters (cross-sectional area, cortical thickness, and buckling ratio) were linked to a broad region on chromosome 20p12-q12 with LOD scores ranging from 1.95 to 2.29. A candidate gene called bone morphogenetic protein 2 (BMP2) is located in that region.
BMP2 is known to regulate bone growth and in a recent study was identified as a genetic determinant of risk for osteoporosis (PLoS Biol. 2003;1:E69).
The researchers also observed some difference in the linkages for buckling ratio and cortical thickness between males and females. “Taken together, this evidence suggests a gene or a group of genes appearing in this area may have significant effects on [bone mineral density], bone geometry, and probably other fracture-related factors,” said Mr. Shen, a doctoral student at Creighton's Osteoporosis Research Center.
The meeting was sponsored by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the American Society for Bone and Mineral Research.