Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
J Bone Miner Res. 2012 Apr;27(4):954-8. doi: 10.1002/jbmr.1537.
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.
遗传因素可能导致椎体骨折的风险；然而，关于椎体骨折（VFrx）、椎体体积骨矿物质密度（vBMD）和几何形状的遗传贡献的研究较少。此外，VFrx 的遗传率（h(2)）及其与 VFrx 风险相关表型的遗传相关性尚未确定。本研究旨在估计欧洲裔三代弗雷明汉心脏研究（FHS）家族成员的椎体骨折、vBMD 和来自定量计算机断层扫描（QCT）的横截面积（CSA）的 h(2)，并估计它们在多大程度上共享常见的遗传关联。FHS 家族的成员通过侧位射线照相或 QCT 侧视视图在 13 个椎体水平（T(4)至 L(4)）使用 Genant 的半定量（SQ）量表（等级 0 至 3）评估 VFrx。椎体骨折定义为任何椎体高度至少减少 25%。我们还分析了 L(3)水平的积分（In.BMD）和小梁（Tb.BMD）vBMD 和 CSA 的 QCT 扫描。计算了遗传率估计值，并进行了双变量遗传相关性分析，调整了各种协变量。对于 VFrx，我们分析了包括 2082 名女性和 2017 名男性在内的 4099 名个体（148 例 VFrx 病例），来自三代。未经调整和多变量调整的 h(2)估计值为 0.43 至 0.69（p < 1.1 × 10(-2)）。共有包括 1737 名男性和 1596 名女性在内的 3333 名个体来自两代人，具有 VFrx 状态和 QCT 衍生的 vBMD 和 CSA 信息。未经调整和多变量调整的 vBMD 和 CSA 的 h(2)估计值范围为 0.27 至 0.51。在双变量分析中，VFrx 与多变量调整后的 In.BMD（-0.22）和 Tb.BMD（-0.29）之间存在中度遗传相关性。我们的研究表明，欧洲裔成年人的椎体骨折、椎体 vBMD 和 CSA 是可遗传的，这强调了进一步工作的重要性，以确定与椎体骨折、骨密度和几何形状遗传易感性相关的特定变体。
