Cell adhesion molecule pathway genes are regulated by cis-regulatory SNPs and show significantly altered expression in Alzheimer's disease brains
Cell adhesion molecule pathway genes are regulated by cis-regulatory SNPs and show significantly altered expression in Alzheimer's disease brains
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DOI：
10.1016/j.neurobiolaging.2015.06.006
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发表时间：
2015-10-01
影响因子：
4.2
通讯作者：
Liu, Guiyou
中科院分区：
文献类型：
--
作者：
Bao, Xinjie;Liu, Gengfeng;Liu, Guiyou
我们之前在2项阿尔茨海默病（AD）全基因组关联研究（GWAS）中发现细胞粘附分子（CAM）途径是一致的信号。然而，CAM途径在AD中的遗传机制尚不清楚。在这里，我们使用(1)京都基因与基因组百科全书和基因本体路径进行路径分析；(2) 4个脑表达GWAS数据集；(3) 2个全基因组AD病例对照表达数据集。使用4个脑表达GWAS数据集，我们发现由顺式调节性单核苷酸多态性（snp）调控的基因在CAM途径中显著富集（p = 2.05E-06, p = 6.10E-07, p = 2.05E-06和p = 1.47E-07）。有趣的是，CAM是一个显著富集的通路，使用数据集5中的下调基因（原始p = 0.0235，调整p = 0.0305）和所有差异表达基因（原始p = 0.0105，调整p = 0.0156），以及数据集6中的所有差异表达基因（原始p = 0.0041，调整p = 0.0062）。综上所述，我们的研究结果表明CAM途径基因受顺式调控snp的调控，并且在AD中表达显著改变。我们相信我们的结果促进了对阿尔茨海默病机制的理解，并将对未来阿尔茨海默病的遗传研究有用。(C) 2015爱思唯尔公司版权所有。
We previously identified the cell adhesion molecule (CAM) pathway as a consistent signal in 2 Alzheimer's disease (AD) genome-wide association studies (GWAS). However, the genetic mechanisms of the CAM pathway in AD are unclear. Here, we conducted pathway analysis using (1) Kyoto Encyclopedia of Genes and Genomes and Gene Ontology pathways; (2) 4 brain expression GWAS datasets; and (3) 2 whole-genome AD case-control expression datasets. Using the 4 brain expression GWAS datasets, we identified that genes regulated by cis-regulatory single-nucleotide polymorphisms (SNPs) were significantly enriched in the CAM pathway (p = 2.05E-06, p = 6.10E-07, p = 2.05E-06, and p = 1.47E-07 for each dataset). Interestingly, CAM is a significantly enriched pathway using down-regulated genes (raw p = 0.0235 and adjusted p = 0.0305) and all differentially expressed genes (raw p = 0.0105 and adjusted p = 0.0156) in dataset 5, and all differentially expressed genes (raw p = 0.0041 and adjusted p = 0.0062) in dataset 6. Collectively, our results show that CAM pathway genes are regulated by cis-regulatory SNPs and show significantly altered expression in AD. We believe that our results advance the understanding of AD mechanisms and will be useful for future genetic studies of AD. (C) 2015 Elsevier Inc. All rights reserved.