荟萃分析确定 MECOM 基因是骨质疏松性骨折的一个新的易感因素。
Meta-analysis identifies a MECOM gene as a novel predisposing factor of osteoporotic fracture.
机构信息
Center for Genome Science, National Institute of Health, Chungcheongbuk-do, Republic of Korea.
出版信息
J Med Genet. 2013 Apr;50(4):212-9. doi: 10.1136/jmedgenet-2012-101156. Epub 2013 Jan 24.
BACKGROUND
Osteoporotic fracture (OF) as a clinical endpoint is a major complication of osteoporosis. To screen for OF susceptibility genes, we performed a genome-wide association study and carried out de novo replication analysis of an East Asian population.
METHODS
Association was tested using a logistic regression analysis. A meta-analysis was performed on the combined results using effect size and standard errors estimated for each study.
RESULTS
In a combined meta-analysis of a discovery cohort (288 cases and 1139 controls), three hospital based sets in replication stage I (462 cases and 1745 controls), and an independent ethnic group in replication stage II (369 cases and 560 for controls), we identified a new locus associated with OF (rs784288 in the MECOM gene) that showed genome-wide significance (p=3.59×10(-8); OR 1.39). RNA interference revealed that a MECOM knockdown suppresses osteoclastogenesis.
CONCLUSIONS
Our findings provide new insights into the genetic architecture underlying OF in East Asians.
背景
骨质疏松性骨折（OF）作为一个临床终点是骨质疏松症的主要并发症。为了筛选 OF 易感基因，我们进行了全基因组关联研究，并对东亚人群进行了从头复制分析。
方法
使用逻辑回归分析进行关联测试。使用为每项研究估计的效应大小和标准误差对合并结果进行荟萃分析。
结果
在一项发现队列（288 例和 1139 例对照）的综合荟萃分析中，在复制阶段 I（462 例和 1745 例对照）的三个基于医院的数据集，以及在复制阶段 II 的一个独立族群（369 例和 560 例对照）中，我们确定了一个与 OF 相关的新基因座（MECOM 基因中的 rs784288），其显示出全基因组显著意义（p=3.59×10(-8)；OR 1.39）。RNA 干扰显示 MECOM 敲低可抑制破骨细胞形成。
结论
我们的研究结果为东亚人群中 OF 的遗传结构提供了新的见解。
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