The Key Laboratory of Biomedical Information Engineering of Ministry of Education and Institute of Molecular Genetics, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi 710049, PR China.
Bone. 2010 Jan;46(1):129-36. doi: 10.1016/j.bone.2009.09.025. Epub 2009 Sep 26.
Femoral neck (FN) bone geometry is an important predictor of bone strength with high heritability. Previous studies have revealed certain candidate genes for FN bone geometry. However, the majority of the underlying genetic factors remain to be discovered. In this study, pathway-based genome-wide association analysis was performed to explore the joint effects of genes within biological pathways on FN bone geometry variations in a cohort of 1000 unrelated US whites. Nominal significant associations (nominal p value<0.05) were observed between 76 pathways and a key FN bone geometry variable-section modulus (Z), biomechanically indicative of bone strength subject to bending. Among them, EphrinA-EphR pathway was most significantly associated with FN Z even after multiple testing adjustments (p(FWER) value=0.035). The association of EphrinA-EphR pathway with FN Z was also observed in an independent sample from Framingham Osteoporosis Study. Overall, these results suggest the significant genetic contribution of EphrinA-EphR pathway to femoral neck bone geometry.
股骨颈（FN）骨几何形状是骨骼强度的一个重要预测因子，具有高度遗传性。先前的研究已经揭示了某些候选基因与 FN 骨几何形状有关。然而，大多数潜在的遗传因素仍有待发现。在这项研究中，进行了基于途径的全基因组关联分析，以探讨生物途径内的基因对 1000 名美国白人无关个体 FN 骨几何形状变量-截面模数（Z）变化的联合影响。Z 值是生物力学上表示骨骼在弯曲时的强度的一个关键 FN 骨几何形状变量，在该研究中观察到 76 个途径与 Z 值之间存在显著的名义关联（名义 p 值<0.05）。即使在经过多次测试调整后（FWER 值=0.035），EphrinA-EphR 途径与 FN Z 值之间的关联仍然最为显著。在弗雷明汉骨质疏松症研究的另一个独立样本中也观察到 EphrinA-EphR 途径与 FN Z 值之间的关联。总体而言，这些结果表明 EphrinA-EphR 途径对股骨颈骨几何形状有重要的遗传贡献。
