Cortical bone health shows significant linkage to chromosomes 2p, 3p, and 17q in 10-year-old children.

Abstract

Genes play an important role in lifelong skeletal health. Genes that influence bone building during childhood have the potential to affect bone health not only throughout childhood but also into adulthood. Given that peak bone mass is a significant predictor of adult fracture risk, it is imperative that the genetic underpinnings of the normal pediatric skeleton are uncovered. In a sample of 600 10-year-old children from 144 families in the Fels Longitudinal Study, we examined radiographic cortical bone measures of the second metacarpal. Morphometic measurements included bone width, medial and lateral cortical thicknesses, and the calculated cortical index representing the amount of cortex relative to bone width. We then conducted genome-wide linkage analysis on these traits in 440 genotyped individuals using the SOLAR analytic platform. Significant quantitative trait loci (QTL) were identified for bone traits on three separate chromosomes. A QTL for medial cortical thickness was localized to chromosome 2p25.2. A QTL for lateral cortical thickness was localized to chromosomal region 3p26.1-3p25.3. Finally, a QTL detected for cortical index was localized to the 17q21.2 chromosomal region. Each region contains plausible candidate genes for pediatric skeletal health, some of which confirm findings from studies of adulthood bone, and for others represent novel candidate genes for skeletal health.