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Identifying the Association Between Alzheimer’s Disease and Parkinson’s Disease Using Genome-Wide Association Studies and Protein-Protein Interaction Network

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Abstract

Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the first and second most common neurodegenerative diseases in the elderly. Shared clinical and pathological features have been reported. Recent large-scale genome-wide association studies (GWAS) have been conducted and reported a number of AD and PD variants. Until now, the underlying genetic mechanisms for all these newly identified PD variants as well as the association between AD and PD are still unclear exactly. We think that PD variants may contribute to AD and PD by influence on brain gene expression. Here, we conducted a systems analysis using (1) AD and PD variants (P < 5.00E−08) identified by the published GWAS; (2) four brain expression GWAS datasets using expression quantitative trait loci from the cerebellum and temporal cortex; (3) large-scale AD GWAS from the Alzheimer Disease Genetics Consortium (ADGC); (4) a protein-protein interaction network. Our results indicated that PD variants around the 17q21 were associated with gene expression and suggestive AD risk. We also identified significant interaction among AD and PD susceptibility genes. We believe that our findings may explain the underlying genetic mechanisms for newly identified PD variants in PD and AD, as well as the association between AD and PD, which may be very useful for future genetic studies for both diseases.

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Acknowledgments

Authors thank NHGRI GWAS catalog, Do et al., Pankratz et al., Nalls, and Zou et al. for the GWAS and brain expression GWAS datasets as well as the contribution from Xuling Li in Department of Neurology, Harbin Medical University, Harbin, China. This work was supported by funding from the National Nature Science Foundation of China (Grant Nos. 81300945, 31200934, 31301938, 81471294, 31171219, 81271213, and 81271214) and the National High-Tech Research and Development Project of China (Grant No. 2013AA020106).

Conflict of Interest

The authors declare no conflict of interests.

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Authors and Affiliations

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

    Guiyou Liu, Guoda Ma, Bin Zhao & Keshen Li

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

    Guiyou Liu

  3. Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China

    Xinjie Bao & Renzhi Wang

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

    Yongshuai Jiang

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

    Mingzhi Liao

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

    Qinghua Jiang

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

    Rennan Feng

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

    Liangcai Zhang

  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

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  1. Guiyou Liu
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  2. Xinjie Bao
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  5. Qinghua Jiang
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  10. Guangyu Wang
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  11. Renzhi Wang
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  12. Bin Zhao
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  13. Keshen Li
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Corresponding authors

Correspondence to Renzhi Wang, Bin Zhao or Keshen Li.

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Guiyou Liu and Xinjie Bao contributed equally to this work.

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Liu, G., Bao, X., Jiang, Y. et al. Identifying the Association Between Alzheimer’s Disease and Parkinson’s Disease Using Genome-Wide Association Studies and Protein-Protein Interaction Network. Mol Neurobiol 52, 1629–1636 (2015). https://doi.org/10.1007/s12035-014-8946-8

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