Molecular Neurobiology

, Volume 54, Issue 1, pp 594–600 | Cite as

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

  • Qinghua Jiang
  • Shuilin Jin
  • Yongshuai Jiang
  • Mingzhi Liao
  • Rennan Feng
  • Liangcai Zhang
  • Guiyou LiuEmail author
  • Junwei Hao


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.


Genome-wide association study Alzheimer’s disease Pathway analysis Immune pathways Immune cells 



This work was supported by funding from the National Nature Science Foundation of China (Grant Nos. 81300945 and 61571152).

Compliance with Ethical Standard

Conflict of Interest

The authors reported no potential conflicts of interest.

Supplementary material

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Supplementary Table 1 (XLS 88 kb)
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Supplementary Table 2 (XLS 250 kb)
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Supplementary Table 3 (XLS 43 kb)


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Qinghua Jiang
    • 1
  • Shuilin Jin
    • 2
  • Yongshuai Jiang
    • 3
  • Mingzhi Liao
    • 3
  • Rennan Feng
    • 4
  • Liangcai Zhang
    • 5
  • Guiyou Liu
    • 1
    • 6
    Email author
  • Junwei Hao
    • 7
  1. 1.School of Life Science and TechnologyHarbin Institute of TechnologyHarbinChina
  2. 2.Department of MathematicsHarbin Institute of TechnologyHarbinChina
  3. 3.College of Bioinformatics Science and TechnologyHarbin Medical UniversityHarbinChina
  4. 4.Department of Nutrition and Food Hygiene, School of Public HealthHarbin Medical UniversityHarbinChina
  5. 5.Department of StatisticsRice UniversityHoustonUSA
  6. 6.Genome Analysis Laboratory, Tianjin Institute of Industrial BiotechnologyChinese Academy of SciencesTianjinChina
  7. 7.Department of Neurology and Tianjin Neurological InstituteTianjin Medical University General HospitalTianjinChina

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