deCODE genetics/Amgen Inc., Reykjavik, 101, Iceland.
Faculty of Medicine, University of Iceland, Reykjavik, 101, Iceland.
Nat Commun. 2019 May 3;10(1):2054. doi: 10.1038/s41467-019-09860-0.
Bone area is one measure of bone size that is easily derived from dual-energy X-ray absorptiometry (DXA) scans. In a GWA study of DXA bone area of the hip and lumbar spine (N ≥ 28,954), we find thirteen independent association signals at twelve loci that replicate in samples of European and East Asian descent (N = 13,608 - 21,277). Eight DXA area loci associate with osteoarthritis, including rs143384 in GDF5 and a missense variant in COL11A1 (rs3753841). The strongest DXA area association is with rs11614913[T] in the microRNA MIR196A2 gene that associates with lumbar spine area (P = 2.3 × 10, β = -0.090) and confers risk of hip fracture (P = 1.0 × 10, OR = 1.11). We demonstrate that the risk allele is less efficient in repressing miR-196a-5p target genes. We also show that the DXA area measure contributes to the risk of hip fracture independent of bone density.
骨面积是衡量骨大小的一个指标，很容易从双能 X 射线吸收法 (DXA) 扫描中得出。在一项针对髋关节和腰椎 DXA 骨面积的全基因组关联研究中（N≥28954），我们在 12 个位点发现了 13 个独立的关联信号，这些信号在欧洲和东亚血统的样本中得到了复制（N=13608-21277）。8 个 DXA 面积位点与骨关节炎相关，包括 GDF5 中的 rs143384 和 COL11A1 中的错义变异（rs3753841）。与 DXA 面积关联最强的是 microRNA MIR196A2 基因中的 rs11614913[T]，它与腰椎面积相关（P=2.3×10，β=-0.090），并增加髋部骨折的风险（P=1.0×10，OR=1.11）。我们证明，风险等位基因在抑制 miR-196a-5p 靶基因方面的效率较低。我们还表明，DXA 面积测量值独立于骨密度，对髋部骨折的风险有贡献。
