PT  - JOURNAL ARTICLE
AU  - Jessica Schulz
AU  - Petros Takousis
AU  - Inken Wohlers
AU  - Ivie O G Itua
AU  - Valerija Dobricic
AU  - Harald Binder
AU  - Lefkos Middleton
AU  - John P A Ioannidis
AU  - Robert Perneczky
AU  - Lars Bertram
AU  - Christina M Lill
TI  - Systematic meta-analyses identify differentially expressed microRNAs in Parkinson’s disease
AID  - 10.1101/253849
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 253849
4099  - http://biorxiv.org/content/early/2018/01/25/253849.short
4100  - http://biorxiv.org/content/early/2018/01/25/253849.full
AB  - MicroRNA-mediated (dys)regulation of gene expression has been implicated in many complex traits including Parkinson’s disease (PD). However, results of microRNA expression studies in PD have been inconclusive. To identify microRNAs that show consistent differential expression in PD, we performed a systematic literature search on microRNA expression studies in PD and extracted extensive data from all eligible publications. After stratification for source of tissue we performed p-value based-meta-analyses across microRNAs assessed in three or more independent datasets. Our literature search screened 459 publications and identified 34 datasets from 27 publications eligible for meta-analysis. On these, we performed 149 meta-analyses on microRNAs quantified in brain (n=124), blood (n=21), or cerebrospinal fluid (CSF) samples (n=4). We identified 15 significantly (Bonferroni-adjusted α=3.36×10−4) differentially expressed microRNAs in brain (n=4) and blood (n=11). Significant findings in brain were observed with hsa-miR-132-3p (p=6.37×10−5), hsa-miR-497-5p (p=1.35×10−4), hsa-miR-628-5p (p=1.67×10−4), and hsa-miR-133b (p=1.90×10−4). The most significant results in blood were observed with hsa-miR-221-3p (p=5.02×10−19), hsa-miR-15b-5p (p=2.49×10−12), and hsa-miR-185-5p (p=4.72×10−11). No significant signals were found in CSF. Analyses of GWAS data for the target genes of the differentially expressed brain microRNAs showed significant association (α=9.40×10−5) of genetic variants in nine loci. Taken together, we identified several microRNAs that showed highly significant differential expression in PD blood and brain. Future studies may assess the possible role of the differentially expressed miRNAs in brain in pathogenesis and disease progression as well as the potential of the top microRNAs in blood as biomarkers for diagnosis, progression or prediction of PD.