Systematic meta-analyses identify differentially expressed microRNAs in Parkinson's disease

Objective: MicroRNA-mediated (dys)regulation of gene expression has been implicated in many disorders including Parkinson9s disease (PD). However, results of microRNA expression studies in PD have been inconclusive. The aim of this study was to identify microRNAs that show consistent differential expression across all published expression studies in PD. Methods: We performed a systematic literature search on microRNA expression studies in PD and extracted data from all eligible publications. After stratification for tissue type we performed meta-analyses across microRNAs assessed in three or more independent datasets. Results: Our literature search screened 459 publications and identified 34 datasets 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 alpha=3.36x10-4) differentially expressed microRNAs in brain (n=4) and blood (n=11). Significant findings in brain were observed with hsa-miR-132-3p (p=6.37x10-5), hsa-miR-497-5p (p=1.35x10-4), hsa-miR-628-5p (p=1.67x10-4), and hsa-miR-133b (p=1.90x10-4). The most significant results in blood were observed with hsa-miR-221-3p (p=5.02x10-19), hsa-miR-15b-5p (p=2.49x10-12), and hsa-miR-185-5p (p=4.72x10-11). No significant signals were found in CSF. Analyses of GWAS data for the target genes of differentially expressed brain microRNAs showed significant association (alpha=9.40x10-5) of genetic variants in nine loci. Interpretation: 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 blood microRNAs as biomarkers for diagnosis, progression or prediction of PD.