Alzheimer’s Disease Variants with the Genome-Wide Significance are Significantly Enriched in Immune Pathways and Active in Immune Cells View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2017-01

AUTHORS

Qinghua Jiang, Shuilin Jin, Yongshuai Jiang, Mingzhi Liao, Rennan Feng, Liangcai Zhang, Guiyou Liu, Junwei Hao

ABSTRACT

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. More... »

PAGES

594-600

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s12035-015-9670-8

DOI

http://dx.doi.org/10.1007/s12035-015-9670-8

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1026166188

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/26746668


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