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Neurobiol Aging. 2015 Oct;36(10):2904.e1-7. doi: 10.1016/j.neurobiolaging.2015.06.006. Epub 2015 Jun 12.

Cell adhesion molecule pathway genes are regulated by cis-regulatory SNPs and show significantly altered expression in Alzheimer's disease brains.

Author information

1
Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
2
The Cadre Ward, The First Hospital of Harbin, Harbin, China.
3
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
4
School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.
5
Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, Harbin, China.
6
Department of Statistics, Rice University, Houston, TX, USA.
7
Institute of Neurology, Guangdong Medical College, Zhanjiang, China.
8
Department of Neurology, The Fourth Affiliated Hospital, Harbin Medical University, Harbin, China.
9
Department of Human Genetics, University of California at Los Angeles, Los Angeles, CA, USA.
10
Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Electronic address: wangrz@126.com.
11
Institute of Neurology, Guangdong Medical College, Zhanjiang, China. Electronic address: keshenli2012@163.com.
12
Genome Analysis Laboratory, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, China. Electronic address: liuguiyou1981@163.com.

Abstract

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.

KEYWORDS:

Alzheimer's disease; Brain expression; Cell adhesion molecules; Genome-wide association studies; Pathway analysis

[Indexed for MEDLINE]

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