Alzheimer's Disease Variants with the Genome-Wide Significance are Significantly Enriched in Immune Pathways and Active in Immune Cells

	Alzheimer's Disease Variants with the Genome-Wide Significance are Significantly Enriched in Immune Pathways and Active in Immune Cells
	Jiang, Qinghua 1; Jin, Shuilin 2; Jiang, Yongshuai 3; Liao, Mingzhi 3; Feng, Rennan 4; Zhang, Liangcai 5; Liu, Guiyou 1,6; Hao, Junwei 7,8
刊名	MOLECULAR NEUROBIOLOGY
	2017
卷号	54 期号:1 页码:594-600
关键词	Genome-wide association study Alzheimer's disease Pathway analysis Immune pathways Immune cells
英文摘要	The existing large-scale genome-wide association studies (GWAS) datasets provide strong support for investigating the mechanisms of Alzheimer's disease (AD) by applying multiple methods of pathway analysis. Previous studies using selected single nucleotide polymorphisms (SNPs) with several thresholds of nominal significance for pathway analysis determined that the threshold chosen for SNPs can reflect the disease model. Presumably, then, pathway analysis with a stringent threshold to define "associated" SNPs would test the hypothesis that highly associated SNPs are enriched in one or more particular pathways. Here, we selected 599 AD variants (P < 5.00E-08) to investigate the pathways in which these variants are enriched and the cell types in which these variants are active. Our results showed that AD variants are significantly enriched in pathways of the immune system. Further analysis indicated that AD variants are significantly enriched for enhancers in a number of cell types, in particular the B-lymphocyte, which is the most substantially enriched cell type. This cell type maintains its dominance among the strongest enhancers. AD SNPs also display significant enrichment for DNase in 12 cell types, among which the top 6 significant signals are from immune cell types, including 4 B cells (top 4 significant signals) and CD14+ and CD34+ cells. In summary, our results show that these AD variants with P < 5.00E-08 are significantly enriched in pathways of the immune system and active in immune cells. To a certain degree, the genetic predisposition for development of AD is rooted in the immune system, rather than in neuronal cells.
WOS标题词	Science & Technology ; Life Sciences & Biomedicine
类目[WOS]	Neurosciences
研究领域[WOS]	Neurosciences & Neurology
关键词[WOS]	ASSOCIATION ; TRAITS ; HUMANS ; SYSTEM ; BACK ; LOCI ; SETS
收录类别	SCI
语种	英语
WOS记录号	WOS:000392133900049
内容类型	期刊论文
源URL	[http://124.16.173.210/handle/834782/2275]
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.Harbin Inst Technol, Sch Life Sci & Technol, Harbin, Peoples R China 2.Harbin Inst Technol, Dept Math, Harbin, Peoples R China 3.Harbin Med Univ, Coll Bioinformat Sci & Technol, Harbin, Peoples R China 4.Harbin Med Univ, Sch Publ Hlth, Dept Nutr & Food Hyg, Harbin, Peoples R China 5.Rice Univ, Dept Stat, Houston, TX 77251 USA 6.Chinese Acad Sci, Tianjin Inst Ind Biotechnol, Genome Anal Lab, Tianjin Airport Econ Area, Xiqi Dao 32, Tianjin 300308, Peoples R China 7.Tianjin Med Univ, Gen Hosp, Dept Neurol, Tianjin, Peoples R China 8.Tianjin Med Univ, Gen Hosp, Tianjin Neurol Inst, Tianjin, Peoples R China
推荐引用方式 GB/T 7714	Jiang, Qinghua,Jin, Shuilin,Jiang, Yongshuai,et al. Alzheimer's Disease Variants with the Genome-Wide Significance are Significantly Enriched in Immune Pathways and Active in Immune Cells[J]. MOLECULAR NEUROBIOLOGY,2017,54(1):594-600.
APA	Jiang, Qinghua.,Jin, Shuilin.,Jiang, Yongshuai.,Liao, Mingzhi.,Feng, Rennan.,...&Hao, Junwei.(2017).Alzheimer's Disease Variants with the Genome-Wide Significance are Significantly Enriched in Immune Pathways and Active in Immune Cells.MOLECULAR NEUROBIOLOGY,54(1),594-600.
MLA	Jiang, Qinghua,et al."Alzheimer's Disease Variants with the Genome-Wide Significance are Significantly Enriched in Immune Pathways and Active in Immune Cells".MOLECULAR NEUROBIOLOGY 54.1(2017):594-600.