Heritability and Genetic Correlations for Bone Microarchitecture: The Framingham Study Families.
Heritability and Genetic Correlations for Bone Microarchitecture: The Framingham Study Families.
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DOI：
10.1002/jbmr.2915
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发表时间：
2017-01
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影响因子：
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通讯作者：
Kiel DP
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作者：
Karasik D;Demissie S;Zhou Y;Lu D;Broe KE;Bouxsein ML;Cupples LA;Kiel DP
高分辨率外周定量计算机断层扫描（HR - pQCT）可测量骨微结构和体积骨矿物质密度（vBMD），它们是骨质疏松性骨折的重要危险因素。我们估算了通过HR - pQCT测量的骨微结构指标和vBMD的遗传力（h²），以及它们之间以及它们与通过双能X线吸收法（DXA）测量的局部骨密度（aBMD）之间的遗传相关性（ρG），研究对象为弗雷明汉心脏研究中的成年亲属。在多达1047名参与者的桡骨远端和胫骨处测量了皮质（Ct）和小梁（Tb）特征，并通过DXA获得了超远端桡骨（UD）的aBMD。在对年龄、性别和雌激素状态（女性）进行调整后，遗传力估计值在桡骨中从19.3%（小梁数量）到82.8%（p < 0.01，Ct.vBMD）不等，在胫骨中从51.9%（小梁厚度）到98.3%（皮质横截面积分数）不等。对身高、体重和桡骨aBMD进行额外调整对h²估计值没有重大影响。在双变量分析中，除皮质孔隙率外，桡骨总vBMD与微结构特征之间存在中等到高度的遗传相关性（ρG从0.227到0.913）。在胫骨中，除皮质孔隙率外，也观察到了类似的遗传相关性模式（ρG从0.274到0.948）。微结构特征之间的环境相关性也很显著。UD aBMD与桡骨处经多变量调整的总vBMD和小梁vBMD之间存在高度遗传相关性（ρG分别为0.811和0.917）。总之，在基于人群队列的相关男性和女性中，桡骨和胫骨的皮质和小梁微结构以及vBMD是可遗传的，并且与通过DXA测量的局部aBMD有一定的h²共享。HR - pQCT特征具有高遗传力的这些发现，在对aBMD进行调整时略有减弱，这支持进一步开展工作以确定长骨体积骨密度和精细结构的特定变异。了解其中一些特征具有遗传相关性有助于减少遗传关联研究中的特征数量。
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 h2 estimates. In bivariate analyses, moderate to high genetic correlations were found between radial total vBMD and microarchitecture traits (ρG from 0.227 to 0.913), except for cortical porosity. At the tibia, a similar pattern of genetic correlations was observed (ρG from 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 h2 with 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.