title: Cell adhesion molecule pathway genes are regulated by cis-regulatory SNPs and show significantly altered expression in Alzheimer's disease brains.
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.
authors.affiliation: Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Xinjie
authors.initials: X
authors.lastname: Bao
authors.affiliation: The Cadre Ward, The First Hospital of Harbin, Harbin, China.
authors.forename: Gengfeng
authors.initials: G
authors.lastname: Liu
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Yongshuai
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Jiang
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Mingzhi
authors.initials: M
authors.lastname: Liao
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, Harbin, China.
authors.forename: Rennan
authors.initials: R
authors.lastname: Feng
authors.affiliation: Department of Statistics, Rice University, Houston, TX, USA.
authors.forename: Liangcai
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Institute of Neurology, Guangdong Medical College, Zhanjiang, China.
authors.forename: Guoda
authors.initials: G
authors.lastname: Ma
authors.affiliation: Department of Neurology, The Fourth Affiliated Hospital, Harbin Medical University, Harbin, China.
authors.forename: Shuyan
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Human Genetics, University of California at Los Angeles, Los Angeles, CA, USA.
authors.forename: Zugen
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Institute of Neurology, Guangdong Medical College, Zhanjiang, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhao
authors.affiliation: 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.
authors.forename: Renzhi
authors.initials: R
authors.lastname: Wang
authors.affiliation: Institute of Neurology, Guangdong Medical College, Zhanjiang, China. Electronic address: keshenli2012@163.com.
authors.forename: Keshen
authors.initials: K
authors.lastname: Li
authors.affiliation: Genome Analysis Laboratory, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, China. Electronic address: liuguiyou1981@163.com.
authors.forename: Guiyou
authors.initials: G
authors.lastname: Liu
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics*; D001921:Brain; D066264:Datasets as Topic; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D019006:Neural Cell Adhesion Molecules / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics*
chemical_list: D019006:Neural Cell Adhesion Molecules
keywords: Alzheimer's disease; Brain expression; Cell adhesion molecules; Genome-wide association studies; Pathway analysis