Imperial College London

DrAbbasDehghan

Faculty of MedicineSchool of Public Health

Reader in Cardiometabolic Disease Epidemiology
 
 
 
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Contact

 

+44 (0)20 7594 3347a.dehghan CV

 
 
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Location

 

157Norfolk PlaceSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Ghanbari:2016:10.1038/srep28387,
author = {Ghanbari, M and Ikram, MA and De, Looper HWJ and Hofman, A and Erkeland, SJ and Franco, OH and Dehghan, A},
doi = {10.1038/srep28387},
journal = {Scientific Reports},
title = {Genome-wide identification of microRNA-related variants associated with risk of Alzheimer's disease},
url = {http://dx.doi.org/10.1038/srep28387},
volume = {6},
year = {2016}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - MicroRNAs (miRNAs) serve as key post-Transcriptional regulators of gene expression. Genetic variation in miRNAs and miRNA-binding sites may affect miRNA function and contribute to disease risk. Here, we investigated the extent to which variants within miRNA-related sequences could constitute a part of the functional variants involved in developing Alzheimer's disease (AD), using the largest available genome-wide association study of AD. First, among 237 variants in miRNAs, we found rs2291418 in the miR-1229 precursor to be significantly associated with AD (p-value = 6.8 × 10 â '5, OR = 1.2). Our in-silico analysis and in-vitro miRNA expression experiments demonstrated that the variant's mutant allele enhances the production of miR-1229-3p. Next, we found miR-1229-3p target genes that are associated with AD and might mediate the miRNA function. We demonstrated that miR-1229-3p directly controls the expression of its top AD-Associated target gene (SORL1) using luciferase reporter assays. Additionally, we showed that miR-1229-3p and SORL1 are both expressed in the human brain. Second, among 42,855 variants in miRNA-binding sites, we identified 10 variants (in the 3′ UTR of 9 genes) that are significantly associated with AD, including rs6857 that increases the miR-320e-mediated regulation of PVRL2. Collectively, this study shows that miRNA-related variants are associated with AD and suggests miRNA-dependent regulation of several AD genes.
AU - Ghanbari,M
AU - Ikram,MA
AU - De,Looper HWJ
AU - Hofman,A
AU - Erkeland,SJ
AU - Franco,OH
AU - Dehghan,A
DO - 10.1038/srep28387
PY - 2016///
SN - 2045-2322
TI - Genome-wide identification of microRNA-related variants associated with risk of Alzheimer's disease
T2 - Scientific Reports
UR - http://dx.doi.org/10.1038/srep28387
UR - http://hdl.handle.net/10044/1/52882
VL - 6
ER -