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MALDI Imaging Mass Spectrometry of Neuropeptides in Parkinson's Disease
Published on: February 14, 2012
Meta-analyses identify differentially expressed micrornas in Parkinson's disease
Jessica Schulz1, Petros Takousis2, Inken Wohlers3
1Genetic and Molecular Epidemiology Group, Lübeck Interdisciplinary Platform for Genome Analytics, Institutes of Neurogenetics & Cardiogenetics, University of Lübeck, Lübeck, Germany.
Objective:
MicroRNA (miRNA)-mediated (dys)regulation of gene expression has been implicated in Parkinson's disease (PD), although results of miRNA expression studies remain inconclusive. We aimed to identify miRNAs that show consistent differential expression across all published expression studies in PD.
Methods:
We performed a systematic literature search on miRNA 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 miRNAs assessed in three or more independent data sets. Meta-analyses were performed using effect-size- and p-value-based methods, as applicable.
Results:
After screening 599 publications, we identified 47 data sets eligible for meta-analysis. On these, we performed 160 meta-analyses on miRNAs quantified in brain (n = 125), blood (n = 31), or CSF (n = 4). Twenty-one meta-analyses were performed using effect sizes. We identified 13 significantly (Bonferroni-adjusted α = 3.13 × 10-4 ) differentially expressed miRNAs 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 = 6.37 × 10-5 ), hsa-miR-497-5p (p = 1.35 × 10-4 ), and hsa-miR-133b (p = 1.90 × 10-4 ) in brain and with hsa-miR-221-3p (p = 4.49 × 10-35 ), hsa-miR-214-3p (p = 2.00 × 10-34 ), and hsa-miR-29c-3p (p = 3.00 × 10-12 ) in blood. No significant signals were found in CSF. Analyses of genome-wide association study data for target genes of brain miRNAs showed significant association (α = 9.40 × 10-5 ) of genetic variants in nine loci.
Interpretation:
We identified several miRNAs 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 miRNAs as biomarkers for diagnosis, progression, or prediction of PD. ANN NEUROL 2019;85:835-851.
Insights
This study identified consistently differentially expressed microRNAs (miRNAs) in Parkinson's disease (PD) brain and blood samples. These findings may help understand PD pathogenesis and develop diagnostic biomarkers.
Area of Science:
- Neuroscience
- Genetics
- Molecular Biology
Background:
- MicroRNA (miRNA) dysregulation is linked to Parkinson's disease (PD), but study results are inconsistent.
- Identifying consistently expressed miRNAs is crucial for understanding PD pathogenesis and developing diagnostic tools.
Purpose of the Study:
- To identify microRNAs (miRNAs) with consistent differential expression across all published Parkinson's disease (PD) studies.
- To analyze miRNA expression in brain, blood, and cerebrospinal fluid (CSF) samples from PD patients.
Main Methods:
- Systematic literature search of miRNA expression studies in PD.
- Meta-analysis of eligible publications, stratifying data by specimen type (brain, blood, CSF).
- Analysis of miRNA expression using effect-size and p-value based methods across studies with three or more data sets.
Main Results:
- 160 meta-analyses were performed on 47 datasets, identifying 13 significantly differentially expressed miRNAs in brain (3) and blood (10).
- Top brain miRNAs include hsa-miR-132-3p, hsa-miR-497-5p, and hsa-miR-133b; top blood miRNAs include hsa-miR-221-3p, hsa-miR-214-3p, and hsa-miR-29c-3p.
- No significant miRNA signals were found in CSF. Genome-wide association study data revealed significant associations for target genes of brain miRNAs in nine loci.
Conclusions:
- Several miRNAs exhibit significant differential expression in Parkinson's disease (PD).
- Brain miRNAs may play a role in PD pathogenesis and progression.
- Blood miRNAs show potential as biomarkers for PD diagnosis, progression, or prediction.
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