Heritability of calcaneal quantitative ultrasound measures in healthy adults from the Fels Longitudinal Study

Abstract

Quantitative ultrasound (QUS) measurements of bone have been reported to predict osteoporotic fracture risk in postmenopausal women and older men. Although many studies have examined the heritability of bone mineral density (BMD), few studies have estimated the heritability of calcaneal QUS phenotypes. In the present study, we examined the genetic regulation of calcaneal QUS parameters in individuals from nuclear and extended families. The study population includes 260 men and 295 women aged 18–91 years (mean ± SD: 46 ± 16 years) who belong to 111 pedigrees in the Fels Longitudinal Study. Three measures of calcaneal structure were collected from both the right and left heel using the Sahara® bone sonometer. These measures included broadband ultrasound attenuation (BUA), speed of sound (SOS), and the quantitative ultrasound index (QUI). We used a variance components based maximum likelihood method to estimate the heritability of QUS parameters while simultaneously adjusting for covariate effects. Additionally, we used bivariate extensions of these methods to calculate additive genetic and random environmental correlations among QUS measures. All phenotypes demonstrated statistically significant heritabilities ( P < 0.0000001). Heritabilities in the right heel ( h 2 ± SE) were h 2 = 0.59 ± 0.10 for BUA, h 2 = 0.73 ± 0.09 for SOS, and h 2 = 0.72 ± 0.09 for QUI. Similarly, heritabilities for the left heel were h 2 = 0.52 ± 0.10, h 2 = 0.75 ± 0.10, and h 2 = 0.70 ± 0.10, respectively. There was evidence for significant genetic and environmental correlations among these six QUS measures. Combinations of QUS measures in the right and left heel demonstrated genetic correlations of 0.94–0.99 and all were significantly different from one indicating at least a partially unique genetic architecture for each of these measures. This study demonstrates that QUS measures of the calcaneus among healthy men and women are heritable, and there are large shared additive genetic effects among all of the traits examined.