Cell adhesion molecules contribute to Alzheimer's disease: multiple pathway analyses of two genome-wide association studies

	Cell adhesion molecules contribute to Alzheimer's disease: multiple pathway analyses of two genome-wide association studies
	Liu, Guiyou 1; Jiang, Yongshuai 2; Wang, Ping ; Feng, Rennan 3; Jiang, Nan ; Chen, Xiaoyun ; Song, Hui ; Chen, Zugen 4
刊名	JOURNAL OF NEUROCHEMISTRY
	2012
卷号	120 期号:1 页码:190-198
关键词	Alzheimer's disease cell adhesion molecules complex neurological disorder genome-wide association studies multiple testing correction pathway analysis
英文摘要	Alzheimers disease (AD) is a kind of complex neurological disorder. The complex genetic architecture of AD makes genetic analysis difficult. Fortunately, a pathway-based method to study the existing genome-wide association studies datasets has been applied into AD. However, no shared Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway was reported. In this study, we performed multiple pathway analyses of French AD genome-wide association studies dataset (discovery dataset, n = 7360, 2032 cases and 5328 controls) and Pfizer dataset (validation dataset, n = 2220, 1034 cases and 1186 controls). First, we performed multiple pathway analyses by Hypergeometric test, improved gene set enrichment analysis (IGSEA) and Z-statistic test in KEGG. Using Hypergeometric test, we identified 54 and 25 significant pathways (p < 0.05) in discovery dataset and validation dataset, respectively. Using IGSEA method, we identified three significant pathways in both discovery and validation datasets, respectively. Using Z-statistic test, we identified 19 significant pathways in validation dataset. Among the significant pathways, cell adhesion molecules (CAM) pathway was identified to be the only consistent signal emerging across multiple analyses in KEGG. After permutation and multiple testing corrections, CAM pathway was significant with p = 2.40E-05 (Hypergeometric test) and p = 3.00E-03 (IGSEA) in discovery dataset. In validation dataset, CAM pathway was significant with p = 1.84E-06 (Hypergeometric test), p = 1.00E-02 (IGSEA) and p = 2.81E-03 (Z-statistic test). We replicated the association by multiple pathway analyses in Gene Ontology using Hypergeometric test (WebGestalt), modified Fishers exact test (DAVID) and Binomial test (PANTHER). Our findings provided further evidence on the association between CAM pathway and AD susceptibility, which would be helpful to study the genetic mechanisms of AD and may significantly assist in the development of therapeutic strategies.
WOS标题词	Science & Technology ; Life Sciences & Biomedicine
类目[WOS]	Biochemistry & Molecular Biology ; Neurosciences
研究领域[WOS]	Biochemistry & Molecular Biology ; Neurosciences & Neurology
关键词[WOS]	AMYLOID PRECURSOR PROTEIN ; AUTISM SPECTRUM DISORDER ; GENE SET ENRICHMENT ; IDENTIFIES VARIANTS ; EXPRESSION ; SYSTEM ; LOCI ; CLU ; NEURODEGENERATION ; INFLAMMATION
收录类别	SCI
语种	英语
WOS记录号	WOS:000298060500019
公开日期	2011-12-28
内容类型	期刊论文
源URL	[http://localhost/handle/0/197]
专题	天津工业生物技术研究所_基因组分析实验室陈祖耕_期刊论文
作者单位	1.Chinese Acad Sci, Tianjin Inst Ind Biotechnol, Tianjin Airport Econ Area, Tianjin 300308, Peoples R China 2.Harbin Med Coll, Coll Bioinformat Sci & Technol, Harbin, Peoples R China 3.Harbin Med Coll, Sch Publ Hlth, Dept Nutr & Food Hyg, Harbin, Peoples R China 4.Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA USA
推荐引用方式 GB/T 7714	Liu, Guiyou,Jiang, Yongshuai,Wang, Ping,et al. Cell adhesion molecules contribute to Alzheimer's disease: multiple pathway analyses of two genome-wide association studies[J]. JOURNAL OF NEUROCHEMISTRY,2012,120(1):190-198.
APA	Liu, Guiyou.,Jiang, Yongshuai.,Wang, Ping.,Feng, Rennan.,Jiang, Nan.,...&Chen, Zugen.(2012).Cell adhesion molecules contribute to Alzheimer's disease: multiple pathway analyses of two genome-wide association studies.JOURNAL OF NEUROCHEMISTRY,120(1),190-198.
MLA	Liu, Guiyou,et al."Cell adhesion molecules contribute to Alzheimer's disease: multiple pathway analyses of two genome-wide association studies".JOURNAL OF NEUROCHEMISTRY 120.1(2012):190-198.