title: Heritability and Genetic Correlations for Bone Microarchitecture: The Framingham Study Families.
abstract: High-resolution peripheral quantitative computed tomography (HR-pQCT) measures bone microarchitecture and volumetric bone mineral density (vBMD), important risk factors for osteoporotic fractures. We estimated the heritability (h2) of bone microstructure indices and vBMD, measured by HR-pQCT, and genetic correlations (ρG) among them and between them and regional aBMD measured by dual-energy X-ray absorptiometry (DXA), in adult relatives from the Framingham Heart Study. Cortical (Ct) and trabecular (Tb) traits were measured at the distal radius and tibia in up to 1047 participants, and ultradistal radius (UD) aBMD was obtained by DXA. Heritability estimates, adjusted for age, sex, and estrogenic status (in women), ranged from 19.3% (trabecular number) to 82.8% (p < 0.01, Ct.vBMD) in the radius and from 51.9% (trabecular thickness) to 98.3% (cortical cross-sectional area fraction) in the tibia. Additional adjustments for height, weight, and radial aBMD had no major effect on h2estimates. In bivariate analyses, moderate to high genetic correlations were found between radial total vBMD and microarchitecture traits (ρGfrom 0.227 to 0.913), except for cortical porosity. At the tibia, a similar pattern of genetic correlations was observed (ρGfrom 0.274 to 0.948), except for cortical porosity. Environmental correlations between the microarchitecture traits were also substantial. There were high genetic correlations between UD aBMD and multivariable-adjusted total and trabecular vBMD at the radius (ρG= 0.811 and 0.917, respectively). In summary, in related men and women from a population-based cohort, cortical and trabecular microarchitecture and vBMD at the radius and tibia were heritable and shared some h2with regional aBMD measured by DXA. These findings of high heritability of HR-pQCT traits, with a slight attenuation when adjusting for aBMD, supports further work to identify the specific variants underlying volumetric bone density and fine structure of long bones. Knowledge that some of these traits are genetically correlated can serve to reduce the number of traits for genetic association studies. © 2016 American Society for Bone and Mineral Research.
authors.affiliation: Institute for Aging Research, Hebrew SeniorLife, Boston, MA, USA.|Faculty of Medicine, Bar Ilan University, Safed, Israel.
authors.forename: David
authors.initials: D
authors.lastname: Karasik
authors.affiliation: Biostatistics, Boston University School of Public Health, Boston, MA, USA.
authors.forename: Serkalem
authors.initials: S
authors.lastname: Demissie
authors.affiliation: Biostatistics, Boston University School of Public Health, Boston, MA, USA.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Biostatistics, Boston University School of Public Health, Boston, MA, USA.
authors.forename: Darlene
authors.initials: D
authors.lastname: Lu
authors.affiliation: Institute for Aging Research, Hebrew SeniorLife, Boston, MA, USA.
authors.forename: Kerry E
authors.initials: KE
authors.lastname: Broe
authors.affiliation: Center for Advanced Orthopedic Studies, Beth Israel Deaconess Medical Center, Boston, MA, USA.|Harvard Medical School, Boston, MA, USA.
authors.forename: Mary L
authors.initials: ML
authors.lastname: Bouxsein
authors.affiliation: Institute for Aging Research, Hebrew SeniorLife, Boston, MA, USA.|Framingham Heart Study, Framingham, MA, USA.
authors.forename: L Adrienne
authors.initials: LA
authors.lastname: Cupples
authors.affiliation: Institute for Aging Research, Hebrew SeniorLife, Boston, MA, USA.|Harvard Medical School, Boston, MA, USA.|Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
authors.forename: Douglas P
authors.initials: DP
authors.lastname: Kiel
mesh_terms: D015502:Absorptiometry, Photon; D000368:Aged; D015519:Bone Density; D001842:Bone and Bones / Q000033:anatomy & histology* / Q000000981:diagnostic imaging; D005190:Family; D005260:Female; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics*; D008297:Male; D019655:Quantitative Trait, Heritable; D014057:Tomography, X-Ray Computed
keywords: BONE QCT/MICRO-CT; CORTICAL POROSITY; GENERAL POPULATION STUDIES; GENETIC EPIDEMIOLOGICAL STUDY; HERITABILITY