title: An investigation of unique and shared gene effects on speed of sound and bone density using axial transmission quantitative ultrasound and DXA in twins.
abstract: The genetic influences of speed of sound (SOS) and BMD were evaluated using 215 pairs of healthy female twins. Genetic influences were found for all SOS and BMD measurements. A combination of shared and unique genetic influences was found to control BMD and SOS at the radius.
  
  
  BACKGROUND
  The aim of this study was to investigate to what extent axial transmission speed of sound (SOS) measurements in cortical bone at multiple, peripheral skeletal sites will be influenced by genetic factors and to estimate the proportion of shared and unique genetic influences controlling bone mineral density (BMD) and SOS at a single site, the radius.
  
  
  METHODS
  The study population consisted of 215 pairs of healthy female twins. Of these, 85 pairs were monozygotic (MZ) and 130 pairs were dizygotic (DZ). The twins had measurements of the nondominant third proximal phalanx, one-third radius, midshaft tibia, and fifth metatarsal using the Sunlight Omnisense and DXA measurements of the lumbar spine, nondominant proximal femur, nondominant radius, and whole body using Hologic QDR-4500W densitometers. Calcaneal quantitative ultrasound (QUS) measurements were performed using the McCue CUBA clinical. Intraclass correlations were calculated, and heritability was estimated using multiple regression analysis. Bivariate analysis of site-matched SOS and BMD measurements at the radius was performed using a variance components analysis program.
  
  
  RESULTS
  Age- and body mass index-adjusted heritability estimates ranged from 0.51 (95% CI, 0.32-0.70) to 0.56 (0.37-0.76) for SOS measurements, 0.58 (0.41-0.75) for broadband ultrasound attenuation (BUA), 0.72 (0.58-0.86) to 0.77 (0.63-0.91) for axial BMD, and 0.53 (0.16-0.90) to 0.63 (0.26-1.00) for radius and whole body BMD. The correlation between SOS and DXA at the radius was r = 0.34 (0.29-0.47). Thirty-eight percent (16-57%) of the genetic variance explained by SOS at the radius was also explained by BMD (one-third radius region of interest), with 62% being unique.
  
  
  CONCLUSIONS
  In conclusion, genetic influences were demonstrated for SOS measurements in cortical bone at multiple sites, axial BMD, calcaneal BUA, radius, and whole body BMD. At the radius, up to 38% of the genetic influence is shared by genes controlling BMD and SOS. Clarifying the site specificity and pleiotropic effects of bone genes should help our understanding of these complex pathways.
authors.affiliation: Twin Research and Genetic Epidemiology Unit, St Thomas' Hospital, London, United Kingdom. karen.knapp@kcl.ac.uk
authors.forename: Karen M
authors.initials: KM
authors.lastname: Knapp
authors.forename: Toby
authors.initials: T
authors.lastname: Andrew
authors.forename: Alex J
authors.initials: AJ
authors.lastname: MacGregor
authors.forename: Glen M
authors.initials: GM
authors.lastname: Blake
authors.forename: Ignac
authors.initials: I
authors.lastname: Fogelman
authors.forename: Tim D
authors.initials: TD
authors.lastname: Spector
mesh_terms: D000328:Adult; D015519:Bone Density / Q000235:genetics* / Q000502:physiology*; D001842:Bone and Bones / Q000000981:diagnostic imaging*; D003720:Densitometry; D005260:Female; D006801:Humans; D008682:Metatarsal Bones / Q000000981:diagnostic imaging; D008875:Middle Aged; D011884:Radius / Q000000981:diagnostic imaging; D013977:Tibia / Q000000981:diagnostic imaging; D014429:Twins, Dizygotic / Q000235:genetics*; D014430:Twins, Monozygotic / Q000235:genetics*; D014465:Ultrasonics; D014463:Ultrasonography