TY - JOUR
T1 - Heritability of prevalent vertebral fracture and volumetric bone mineral density and geometry at the lumbar spine in three generations of the framingham study
AU - Liu, Ching Ti
AU - Karasik, David
AU - Zhou, Yanhua
AU - Hsu, Yi Hsiang
AU - Genant, Harry K.
AU - Broe, Kerry E.
AU - Lang, Thomas F.
AU - Samelson, Elizabeth J.
AU - Demissie, Serkalem
AU - Bouxsein, Mary L.
AU - Cupples, L. Adrienne
AU - Kiel, Douglas P.
PY - 2012/4
Y1 - 2012/4
N2 - Genetic factors likely contribute to the risk for vertebral fractures; however, there are few studies on the genetic contributions to vertebral fracture (VFrx), vertebral volumetric bone mineral density (vBMD), and geometry. Also, the heritability (h 2) for VFrx and its genetic correlation with phenotypes contributing to VFrx risk have not been established. This study aims to estimate the h 2 of vertebral fracture, vBMD, and cross-sectional area (CSA) derived from quantitative computed tomography (QCT) scans and to estimate the extent to which they share common genetic association in adults of European ancestry from three generations of Framingham Heart Study (FHS) families. Members of the FHS families were assessed for VFrx by lateral radiographs or QCT lateral scout views at 13 vertebral levels (T 4 to L 4) using Genant's semiquantitative (SQ) scale (grades 0 to 3). Vertebral fracture was defined as having at least 25% reduction in height of any vertebra. We also analyzed QCT scans at the L 3 level for integral (In.BMD) and trabecular (Tb.BMD) vBMD and CSA. Heritability estimates were calculated, and bivariate genetic correlation analysis was performed, adjusting for various covariates. For VFrx, we analyzed 4099 individuals (148 VFrx cases) including 2082 women and 2017 men from three generations. Estimates of crude and multivariable-adjusted h 2 were 0.43 to 0.69 (p<1.1× 10 -2). A total of 3333 individuals including 1737 men and 1596 women from two generations had VFrx status and QCT-derived vBMD and CSA information. Estimates of crude and multivariable-adjusted h 2 for vBMD and CSA ranged from 0.27 to 0.51. In a bivariate analysis, there was a moderate genetic correlation between VFrx and multivariable-adjusted In.BMD (-0.22) and Tb.BMD (-0.29). Our study suggests vertebral fracture, vertebral vBMD, and CSA in adults of European ancestry are heritable, underscoring the importance of further work to identify the specific variants underlying genetic susceptibility to vertebral fracture, bone density, and geometry.
AB - Genetic factors likely contribute to the risk for vertebral fractures; however, there are few studies on the genetic contributions to vertebral fracture (VFrx), vertebral volumetric bone mineral density (vBMD), and geometry. Also, the heritability (h 2) for VFrx and its genetic correlation with phenotypes contributing to VFrx risk have not been established. This study aims to estimate the h 2 of vertebral fracture, vBMD, and cross-sectional area (CSA) derived from quantitative computed tomography (QCT) scans and to estimate the extent to which they share common genetic association in adults of European ancestry from three generations of Framingham Heart Study (FHS) families. Members of the FHS families were assessed for VFrx by lateral radiographs or QCT lateral scout views at 13 vertebral levels (T 4 to L 4) using Genant's semiquantitative (SQ) scale (grades 0 to 3). Vertebral fracture was defined as having at least 25% reduction in height of any vertebra. We also analyzed QCT scans at the L 3 level for integral (In.BMD) and trabecular (Tb.BMD) vBMD and CSA. Heritability estimates were calculated, and bivariate genetic correlation analysis was performed, adjusting for various covariates. For VFrx, we analyzed 4099 individuals (148 VFrx cases) including 2082 women and 2017 men from three generations. Estimates of crude and multivariable-adjusted h 2 were 0.43 to 0.69 (p<1.1× 10 -2). A total of 3333 individuals including 1737 men and 1596 women from two generations had VFrx status and QCT-derived vBMD and CSA information. Estimates of crude and multivariable-adjusted h 2 for vBMD and CSA ranged from 0.27 to 0.51. In a bivariate analysis, there was a moderate genetic correlation between VFrx and multivariable-adjusted In.BMD (-0.22) and Tb.BMD (-0.29). Our study suggests vertebral fracture, vertebral vBMD, and CSA in adults of European ancestry are heritable, underscoring the importance of further work to identify the specific variants underlying genetic susceptibility to vertebral fracture, bone density, and geometry.
KW - QCT
KW - bone mineral density
KW - heritability
KW - vertebral fracture
UR - http://www.scopus.com/inward/record.url?scp=84863375739&partnerID=8YFLogxK
U2 - 10.1002/jbmr.1537
DO - 10.1002/jbmr.1537
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C2 - 22222934
AN - SCOPUS:84863375739
SN - 0884-0431
VL - 27
SP - 954
EP - 958
JO - Journal of Bone and Mineral Research
JF - Journal of Bone and Mineral Research
IS - 4
ER -
