Imperial College London
Alternate

Professor Lefkos Middleton

Faculty of Medicine, School of Public Health

Chair in Clinical Neurology
 
 
 
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Contact

 

+44 (0)20 3311 7290l.middleton CV

 
 
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Assistant

 

Ms Naia Headland-Vanni +44 (0)20 3311 7290

 
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Location

 

Room 10L05 LaboratoryCharing Cross HospitalCharing Cross Campus

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Summary

 

Publications

Citation

BibTex format

@article{Schulz:2019:10.1002/ana.25490,
author = {Schulz, J and Takousis, P and Wohlers, I and Itua, IOG and Dobricic, V and Rücker, G and Binder, H and Middleton, L and Ioannidis, JPA and Perneczky, R and Bertram, L and Lill, CM},
doi = {10.1002/ana.25490},
journal = {Annals of Neurology},
pages = {835--851},
title = {Meta-analyses identify differentially expressed microRNAs in Parkinson's disease},
url = {http://dx.doi.org/10.1002/ana.25490},
volume = {85},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Objective: MicroRNA-mediated (dys)regulation of gene expression has been implicated in Parkinson's disease (PD), although results of microRNA expression studies remain inconclusive. We aimed to identify microRNAs that show consistent differential expression across all published expression studies in PD.Mathods: We performed a systematic literature search on microRNA expression studies in PD and extracted data from eligible publications. After stratification for brain, blood, and cerebrospinal fluid (CSF)-derived specimen we performed meta-analyses across microRNAs assessed in three or more independent datasets. Meta-analyses were performed using effect-size and p-value based methods, as applicable.Results: After screening 599 publications we identified 47 datasets eligible for meta-analysis. On these, we performed 160 meta-analyses on microRNAs quantified in brain (n=125), blood (n=31), or CSF samples (n=4). Twenty-one meta-analyses were performed using effect sizes. We identified 13 significantly (Bonferroni-adjusted α=3.13x10-4 ) differentially expressed microRNAs in brain (n=3) and blood (n=10) with consistent effect directions across studies. The most compelling findings were with hsa-miR-132-3p (p=6.37x10-5 ), hsa-miR-497-5p (p=1.35x10-4 ), and hsa-miR-133b (p=1.90x10-4 ) in brain, and with hsa-miR-221-3p (p=4.49x10-35 ), hsa-miR-214-3p (p=2.00x10-34 ), and hsa-miR-29c-3p (p=3.00x10-12 ) in blood. No significant signals were found in CSF. Analyses of GWAS data for target genes of brain microRNAs showed significant association (α=9.40x10-5 ) of genetic variants in nine loci.Interpretation: We identified several microRNAs that showed highly significant differential expression in PD. Future studies may assess the possible role of the identified brain miRNAs in pathogenesis and disease progression as well as the potential of the top blood microRNAs as biomarkers for diagnosis, progression or prediction of PD.
AU  - Schulz,J
AU  - Takousis,P
AU  - Wohlers,I
AU  - Itua,IOG
AU  - Dobricic,V
AU  - Rücker,G
AU  - Binder,H
AU  - Middleton,L
AU  - Ioannidis,JPA
AU  - Perneczky,R
AU  - Bertram,L
AU  - Lill,CM
DO  - 10.1002/ana.25490
EP  - 851
PY  - 2019///
SN  - 0364-5134
SP  - 835
TI  - Meta-analyses identify differentially expressed microRNAs in Parkinson's disease
T2  - Annals of Neurology
UR  - http://dx.doi.org/10.1002/ana.25490
UR  - https://www.ncbi.nlm.nih.gov/pubmed/30990912
UR  - http://hdl.handle.net/10044/1/69156
VL  - 85
ER  -
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