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Integrating Genome-Wide Association Study and Brain Expression Data Highlights Cell Adhesion Molecules and Purine Metabolism in Alzheimer’s Disease

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Abstract

Alzheimer’s disease (AD) is the most common neurodegenerative disease in the elderly. Recently, genome-wide association studies (GWAS) have been used to investigate AD pathogenesis. However, a large proportion of AD heritability has yet to be explained. We previously identified the cell adhesion molecule (CAM) pathway as a consistent signal in two AD GWAS. However, it is unclear whether CAM is present in the Genetic and Environmental Risk for Alzheimer’s Disease Consortium (GERAD) GWAS and brain expression GWAS. Meanwhile, we think integrating AD GWAS and AD brain expression datasets may provide complementary information to identify important pathways involved in AD. Here, we conducted a systems analysis using (1) KEGG pathways, (2) large-scale AD GWAS from GERAD (n = 11,789), (3) two brain expression GWAS datasets (n = 399) from the AD cerebellum and temporal cortex, and (4) previous results from pathway analysis of AD GWAS. Our results indicate that (1) CAM is a consistent signal in five AD GWAS; (2) CAM is the most significant signal in AD; (3) we confirmed previous AD risk pathways related to immune system and diseases, and cardiovascular disease, etc.; and (4) we highlighted the purine metabolism pathway in AD for the first time. We believe that our results may advance our understanding of AD mechanisms and will be very informative for future genetic studies in AD.

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Acknowledgments

We thank the GERAD Consortium and Zou et al. for the AD GWAS and expression datasets. This work was supported by funding from the National Nature Science Foundation of China (grant numbers 81300945, 31200934, 31301938, 81471294, 31171219, 81271213, 81271214).

Conflict of Interest

The authors declare no conflict of interests.

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Authors and Affiliations

  1. Department of Orthopedic Surgery, Beijing Army General Hospital, Clinical Medicine College of Third Military Medical University, No. 5 Nanmencang, Dongcheng District, Beijing, 100700, China

    Zimin Xiang & Tiansheng Sun

  2. Department of Neurology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China

    Meiling Xu

  3. College of Life Science, Northwest A&F University, Yangling, Shaanxi, China

    Mingzhi Liao

  4. College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China

    Yongshuai Jiang

  5. School of Life Science and Technology, Harbin Institute of Technology, Harbin, China

    Qinghua Jiang

  6. Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, Harbin, China

    Rennan Feng

  7. Department of Statistics, Rice University, Houston, TX, USA

    Liangcai Zhang

  8. Institute of Neurology, Guangdong Medical College, Zhanjiang, 524001, China

    Guoda Ma, Bin Zhao & Keshen Li

  9. Department of Human Genetics, University of California at Los Angeles, Los Angeles, CA, USA

    Zugen Chen

  10. Department of Oncology, The First Hospital of Harbin, Harbin, China

    Guangyu Wang

  11. Genome Analysis Laboratory, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Xiqi Dao 32, Tianjin Airport Economic Area, Tianjin, 300308, China

    Guiyou Liu

Authors
  1. Zimin Xiang
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  2. Meiling Xu
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  3. Mingzhi Liao
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  4. Yongshuai Jiang
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  5. Qinghua Jiang
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  6. Rennan Feng
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  7. Liangcai Zhang
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  8. Guoda Ma
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  9. Guangyu Wang
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  10. Zugen Chen
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  11. Bin Zhao
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  12. Tiansheng Sun
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  13. Keshen Li
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  14. Guiyou Liu
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Corresponding authors

Correspondence to Tiansheng Sun, Keshen Li or Guiyou Liu.

Additional information

Zimin Xiang, Meiling Xu, and Mingzhi Liao contributed equally to this work.

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Xiang, Z., Xu, M., Liao, M. et al. Integrating Genome-Wide Association Study and Brain Expression Data Highlights Cell Adhesion Molecules and Purine Metabolism in Alzheimer’s Disease. Mol Neurobiol 52, 514–521 (2015). https://doi.org/10.1007/s12035-014-8884-5

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  • DOI: https://doi.org/10.1007/s12035-014-8884-5

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