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Molecular Neurobiology

, Volume 53, Issue 7, pp 4931–4938 | Cite as

Convergent Genetic and Expression Datasets Highlight TREM2 in Parkinson’s Disease Susceptibility

  • Guiyou Liu
  • Yongquan Liu
  • Qinghua Jiang
  • Yongshuai Jiang
  • Rennan Feng
  • Liangcai Zhang
  • Zugen Chen
  • Keshen LiEmail author
  • Jiafeng LiuEmail author
Article

Abstract

A rare TREM2 missense mutation (rs75932628-T) was reported to confer a significant Alzheimer’s disease (AD) risk. A recent study indicated no evidence of the involvement of this variant in Parkinson’s disease (PD). Here, we used the genetic and expression data to reinvestigate the potential association between TREM2 and PD susceptibility. In stage 1, using 10 independent studies (N = 89,157; 8787 cases and 80,370 controls), we conducted a subgroup meta-analysis. We identified a significant association between rs75932628 and PD (P = 3.10E-03, odds ratio (OR) = 3.88, 95 % confidence interval (CI) 1.58–9.54) in No-Northern Europe subgroup, and significantly increased PD risks (P = 0.01 for Mann–Whitney test) in No-Northern Europe subgroup than in Northern Europe subgroup. In stage 2, we used the summary results from a large-scale PD genome-wide association study (GWAS; N = 108,990; 13,708 cases and 95,282 controls) to search for other TREM2 variants contributing to PD susceptibility. We identified 14 single-nucleotide polymorphisms (SNPs) associated with PD within 50-kb upstream and downstream range of TREM2. In stage 3, using two brain expression GWAS datasets (N = 773), we identified 6 of the 14 SNPs regulating increased expression of TREM2. In stage 4, using the whole human genome microarray data (N = 50), we further identified significantly increased expression of TREM2 in PD cases compared with controls in human prefrontal cortex. In summary, convergent genetic and expression datasets demonstrate that TREM2 is a potent risk factor for PD and may be a therapeutic target in PD and other neurodegenerative diseases.

Keywords

TREM2 rs75932628 Parkinson’s disease Alzheimer’s disease Genome-wide association study 

Notes

Acknowledgments

This work was supported by funding from the National Nature Science Foundation of China (Grant No. 81300945 and 81471294).

Conflict of interest

The authors reported no potential conflicts of interest.

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Guiyou Liu
    • 1
  • Yongquan Liu
    • 2
  • Qinghua Jiang
    • 3
  • Yongshuai Jiang
    • 4
  • Rennan Feng
    • 5
  • Liangcai Zhang
    • 6
  • Zugen Chen
    • 7
  • Keshen Li
    • 8
    • 9
    Email author
  • Jiafeng Liu
    • 2
    Email author
  1. 1.Genome Analysis Laboratory, Tianjin Institute of Industrial BiotechnologyChinese Academy of SciencesTianjinChina
  2. 2.Department of NeurologyThe First Hospital of HarbinHarbinChina
  3. 3.School of Life Science and TechnologyHarbin Institute of TechnologyHarbinChina
  4. 4.College of Bioinformatics Science and TechnologyHarbin Medical UniversityHarbinChina
  5. 5.Department of Nutrition and Food Hygiene, School of Public Health,Harbin Medical UniversityHarbinChina
  6. 6.Department of StatisticsRice UniversityHoustonUSA
  7. 7.Department of Human GeneticsUniversity of California at Los AngelesLos AngelesUSA
  8. 8.Institute of NeurologyAffiliated Hospital of Guangdong Medical CollegeZhanjiangChina
  9. 9.Stroke Center, Neurology & Neurosurgery Division, The Clinical Medicine Research Institute & The First Affiliated HospitalJinan University GuangzhouGuangzhouChina

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