Meta-analysis identifies a MECOM gene as a novel predisposing factor of osteoporotic fracture.

Meta-analysis identifies a MECOM gene as a novel predisposing factor of osteoporotic fracture.
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荟萃分析将 MECOM 基因确定为骨质疏松性骨折的新诱发因素。

DOI:
10.1136/jmedgenet-2012-101156
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发表时间:
2013-04
影响因子:
4
通讯作者:
Koh JM
Koh JM
中科院分区:
医学1区
文献类型:
--
作者:
Hwang JY;Lee SH;Go MJ;Kim BJ;Kou I;Ikegawa S;Guo Y;Deng HW;Raychaudhuri S;Kim YJ;Oh JH;Kim Y;Moon S;Kim DJ;Koo H;Cha MJ;Lee MH;Yun JY;Yoo HS;Kang YA;Cho EH;Kim SW;Oh KW;Kang MI;Son HY;Kim SY;Kim GS;Han BG;Cho YS;Cho MC;Lee JY;Koh JM

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骨质疏松性骨折(Osteoporotic fracture,OF)是骨质疏松症的主要并发症之一。为了筛选OF易感基因,我们进行了全基因组关联研究,并进行了东亚人群的从头复制分析。使用逻辑回归分析测试关联。使用每项研究估计的效应量和标准误对合并结果进行荟萃分析。在一项对发现队列的综合荟萃分析中,(288例病例和1139例对照),三个基于医院的集,处于复制阶段I(462例和1745对照),和一个独立的种族群体在复制阶段II(369例病例和560例对照),我们确定了一个与OF相关的新位点(MECOM基因中的rs784288),该位点显示出全基因组显著性(p=3.59×10−8; OR 1.39)。RNA干扰表明,MECOM敲低抑制破骨细胞的发生。我们的研究结果提供了新的见解,在东亚人的遗传结构的基础OF。
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. 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. 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. Our findings provide new insights into the genetic architecture underlying OF in East Asians.
DOI: 10.1038/nature10405
发表时间: 2011-09-11
期刊: NATURE
影响因子: 64.8
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