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Alzheimer's Disease Risk Polymorphisms Regulate Gene Expression in the ZCWPW1 and the CELF1 Loci.

Publication ,  Journal Article
Karch, CM; Ezerskiy, LA; Bertelsen, S; Alzheimer’s Disease Genetics Consortium (ADGC), ; Goate, AM
Published in: PLoS One
2016

Late onset Alzheimer's disease (LOAD) is a genetically complex and clinically heterogeneous disease. Recent large-scale genome wide association studies (GWAS) have identified more than twenty loci that modify risk for AD. Despite the identification of these loci, little progress has been made in identifying the functional variants that explain the association with AD risk. Thus, we sought to determine whether the novel LOAD GWAS single nucleotide polymorphisms (SNPs) alter expression of LOAD GWAS genes and whether expression of these genes is altered in AD brains. The majority of LOAD GWAS SNPs occur in gene dense regions under large linkage disequilibrium (LD) blocks, making it unclear which gene(s) are modified by the SNP. Thus, we tested for brain expression quantitative trait loci (eQTLs) between LOAD GWAS SNPs and SNPs in high LD with the LOAD GWAS SNPs in all of the genes within the GWAS loci. We found a significant eQTL between rs1476679 and PILRB and GATS, which occurs within the ZCWPW1 locus. PILRB and GATS expression levels, within the ZCWPW1 locus, were also associated with AD status. Rs7120548 was associated with MTCH2 expression, which occurs within the CELF1 locus. Additionally, expression of several genes within the CELF1 locus, including MTCH2, were highly correlated with one another and were associated with AD status. We further demonstrate that PILRB, as well as other genes within the GWAS loci, are most highly expressed in microglia. These findings together with the function of PILRB as a DAP12 receptor supports the critical role of microglia and neuroinflammation in AD risk.

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Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2016

Volume

11

Issue

2

Start / End Page

e0148717

Location

United States

Related Subject Headings

  • Zinc Fingers
  • Risk Factors
  • Receptors, Immunologic
  • Quantitative Trait Loci
  • Polymorphism, Single Nucleotide
  • Mitochondrial Membrane Transport Proteins
  • Middle Aged
  • Membrane Glycoproteins
  • Male
  • Linkage Disequilibrium
 

Citation

APA
Chicago
ICMJE
MLA
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Karch, C. M., Ezerskiy, L. A., Bertelsen, S., Alzheimer’s Disease Genetics Consortium (ADGC), ., & Goate, A. M. (2016). Alzheimer's Disease Risk Polymorphisms Regulate Gene Expression in the ZCWPW1 and the CELF1 Loci. PLoS One, 11(2), e0148717. https://doi.org/10.1371/journal.pone.0148717
Karch, Celeste M., Lubov A. Ezerskiy, Sarah Bertelsen, Sarah Alzheimer’s Disease Genetics Consortium (ADGC), and Alison M. Goate. “Alzheimer's Disease Risk Polymorphisms Regulate Gene Expression in the ZCWPW1 and the CELF1 Loci.PLoS One 11, no. 2 (2016): e0148717. https://doi.org/10.1371/journal.pone.0148717.
Karch CM, Ezerskiy LA, Bertelsen S, Alzheimer’s Disease Genetics Consortium (ADGC), Goate AM. Alzheimer's Disease Risk Polymorphisms Regulate Gene Expression in the ZCWPW1 and the CELF1 Loci. PLoS One. 2016;11(2):e0148717.
Karch, Celeste M., et al. “Alzheimer's Disease Risk Polymorphisms Regulate Gene Expression in the ZCWPW1 and the CELF1 Loci.PLoS One, vol. 11, no. 2, 2016, p. e0148717. Pubmed, doi:10.1371/journal.pone.0148717.
Karch CM, Ezerskiy LA, Bertelsen S, Alzheimer’s Disease Genetics Consortium (ADGC), Goate AM. Alzheimer's Disease Risk Polymorphisms Regulate Gene Expression in the ZCWPW1 and the CELF1 Loci. PLoS One. 2016;11(2):e0148717.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2016

Volume

11

Issue

2

Start / End Page

e0148717

Location

United States

Related Subject Headings

  • Zinc Fingers
  • Risk Factors
  • Receptors, Immunologic
  • Quantitative Trait Loci
  • Polymorphism, Single Nucleotide
  • Mitochondrial Membrane Transport Proteins
  • Middle Aged
  • Membrane Glycoproteins
  • Male
  • Linkage Disequilibrium