Gene-gene interaction between RBMS3 and ZNF516 influences bone mineral density.
Gene-gene interaction between RBMS3 and ZNF516 influences bone mineral density.
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DOI：
10.1002/jbmr.1788
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发表时间：
2013-04
影响因子：
6.2
通讯作者：
Deng, Hong-Wen
中科院分区：
文献类型：
--
作者：
Yang, Tie-Lin;Guo, Yan;Li, Jian;Zhang, Lei;Shen, Hui;Li, Siyang M.;Li, Siyuan K.;Tian, Qing;Liu, Yong-Jun;Papasian, Christopher J.;Deng, Hong-Wen
骨质疏松症的特点是低骨密度（BMD），这是一种高度遗传的特征，部分由多个基因的作用和相互作用决定。虽然越来越多的基因被发现对骨密度有独立的影响，但很少有研究发现相互作用影响骨密度的基因。在这项研究中，我们在两个独立的美国白种人样本中，对髋部骨密度极高和极低（分布尾部的20%）的个体中选择的候选基因进行了基因相互作用分析。第一个样本包含从2,286名受试者中选出的916名不相关且髋部骨密度z分数极高的受试者。第二个样本由400名不相关的受试者组成，他们的髋部骨密度z分数极高，这些受试者是从1000名受试者中挑选出来的。结合这两个样本的结果，我们发现了一个相互作用的基因对（RBMS3和ZNF516），即使经过多次测试的Bonferroni校正，也显示出对髋关节骨密度的持续显著影响。RMBS3含有两个SNP rs6549904和rs7640046，它们都与位于ZNF516上的SNP rs4891159有显著的相互作用（P值：7.04×10−11和1.03×10−10）。我们在另外两个白种人和非洲人后裔的样本中进一步验证了这些结果。RBMS3与ZNF516基因对在高加索人样本中成功复制（P值：8.07×10−3和2.91×10−3）。对于非洲样本，也检测到显著的相互作用（P值分别为0.031和0.043），但效果的方向与三个高加索样本相反。通过提供骨密度遗传相互作用的证据，本研究进一步描绘了骨质疏松症的遗传结构。
Osteoporosis is characterized by low bone mineral density (BMD), a highly heritable trait that is determined, in part, by the actions and interactions of multiple genes. While an increasing number of genes have been identified to have independent effects on BMD, few studies have been performed to identify genes that interact with one another to affect BMD. In this study, we performed gene-gene interaction analyses in selected candidate genes in individuals with extremely high vs. low hip BMD (20% tails of the distributions), in two independent US Caucasian samples. The first sample contained 916 unrelated subjects with extreme hip BMD Z-scores selected from a population composed of 2,286 subjects. The second sample consisted of 400 unrelated subjects with extreme hip BMD Z-scores selected from a population composed of 1,000 subjects. Combining results from these two samples, we found one interacting gene pair (RBMS3 vs. ZNF516) which, even after Bonferroni correction for multiple testing, showed consistently significant effects on hip BMD. RMBS3 harbored two SNPs, rs6549904 and rs7640046, both of which had significant interactions with a SNP, rs4891159, located on ZNF516 (P values: 7.04×10−11 and 1.03×10−10). We further validated these results in two additional samples of Caucasian and African descent. The gene pair, RBMS3 vs. ZNF516, was successfully replicated in the Caucasian sample (P values: 8.07×10−3 and 2.91×10−3). For the African sample, a significant interaction was also detected (P values: 0.031 and 0.043), but the direction of the effect was opposite to that observed in the three Caucasian samples. By providing evidence for genetic interactions underlying BMD, this study further delineated the genetic architecture of osteoporosis.
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影响因子：
4.1
作者：
Kumar, Jitender;Swanberg, Maria;Akesson, Kristina
通讯作者：
Akesson, Kristina
DOI：
10.1038/nrg2579
发表时间：
2009-06
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
Cordell HJ
通讯作者：
Cordell HJ
影响因子：
30.8
作者：
Marchini, Jonathan;Howie, Bryan;Donnelly, Peter
通讯作者：
Donnelly, Peter
影响因子：
4.5
作者：
Evans, David M.;Marchini, Jonathan;Morris, Andrew P.;Cardon, Lon R.
通讯作者：
Cardon, Lon R.
影响因子：
2.1
作者：
Deng, HW;Mahaney, MC;Recker, RR
通讯作者：
Recker, RR