Meta-analyses identify differentially expressed microRNAs in Parkinson's disease

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