Cited by 132Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchBioinformatics and Genomic Networks

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

Jiang, Qinghua, Jin, Shuilin, Jiang, Yongshuai, Liao, Mingzhi, Feng, Rennan, Zhang, Liangcai, Liu, Guiyou, Hao, Junwei·2017·Molecular Neurobiology

DOI 10.1007/s12035-015-9670-8

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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.

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Authors: Jiang, Q., Jin, S., Jiang, Y., Liao, M., Feng, R., Zhang, L., Liu, G., & Hao, J.
Affiliations: Harbin Institute of Technology (CN)
Harbin Medical University (CN)
Rice University (US)
Chinese Academy of Sciences (CN)
Tianjin Medical University General Hospital (CN)
Corresponding author: Liu, Guiyou
ORCID: Jiang, Qinghua
Jin, Shuilin
Jiang, Yongshuai
Liao, Mingzhi
Feng, Rennan
Liu, Guiyou
Hao, Junwei
Venue: Molecular Neurobiology
Publisher: Springer Science and Business Media LLC
Published: 2016-01-09
Volume: 54
Issue: 1
Pages: 594-600
ISSN: 0893-7648 (ISSN-L)
1559-1182
DOI: 10.1007/s12035-015-9670-8
OpenAlex: W2231149964
Cited by: 132
References: 21
Citations by year: 2026: 1 · 2025: 2 · 2024: 4 · 2023: 2 · 2022: 23 · 2021: 41 · 2020: 5 · 2019: 15 · 2018: 17 · 2017: 14 · 2016: 8
FWCI: 14.47
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Molecular Neurobiology (publishedVersion)
PubMed (publishedVersion)
Funders: National Nature Science Foundation of China (81300945, 61571152)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
Keywords: Alzheimer's disease, genome-wide association study, single nucleotide polymorphisms, pathway enrichment, immune pathways, enhancers, DNase I hypersensitivity, B cells, CD14+ monocytes, CD34+ cells, immune cells, genetic susceptibility, cell type-specific gene expression
MeSH terms: Alzheimer Disease, Humans, Immunity, Cellular, Immune System Diseases, Genetic Variation, Genetic Predisposition to Disease, Databases, Genetic, Genome-Wide Association Study

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

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