荟萃分析确定帕金森病中差异表达的 microRNAs。

Meta-analyses identify differentially expressed micrornas in Parkinson's disease.

机构信息

Genetic and Molecular Epidemiology Group, Lübeck Interdisciplinary Platform for Genome Analytics, Institutes of Neurogenetics & Cardiogenetics, University of Lübeck, Lübeck, Germany.

Ageing Epidemiology Research Unit, School of Public Health, Imperial College, London, United Kingdom.

出版信息

Ann Neurol. 2019 Jun;85(6):835-851. doi: 10.1002/ana.25490.

DOI:10.1002/ana.25490

PMID:30990912

Abstract

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 ) 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 ), hsa-miR-497-5p (p = 1.35 × 10 ), and hsa-miR-133b (p = 1.90 × 10 ) in brain and with hsa-miR-221-3p (p = 4.49 × 10 ), hsa-miR-214-3p (p = 2.00 × 10 ), and hsa-miR-29c-3p (p = 3.00 × 10 ) 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 ) 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.

摘要

目的

微小 RNA（miRNA）介导的基因表达调控在帕金森病（PD）中已有报道，尽管 miRNA 表达研究的结果仍不确定。我们旨在鉴定在所有已发表的 PD 表达研究中均显示出一致差异表达的 miRNA。

方法

我们对 PD 的 miRNA 表达研究进行了系统的文献检索，并从合格的出版物中提取数据。在对源自大脑、血液和脑脊液（CSF）的标本进行分层后，我们对三个或更多独立数据集评估的 miRNA 进行了荟萃分析。荟萃分析使用适用的效应大小和 p 值方法进行。

结果

在筛选了 599 篇文献后，我们确定了 47 个符合荟萃分析条件的数据组。我们对大脑（n = 125）、血液（n = 31）或 CSF（n = 4）中定量的 miRNA 进行了 160 项荟萃分析。21 项荟萃分析使用效应大小进行。我们在大脑（n = 3）和血液（n = 10）中鉴定出 21 个差异表达 miRNA，在研究中具有一致的效应方向，这些 miRNA 经 Bonferroni 调整后，其差异表达具有统计学意义（α = 3.13×10 ）。最引人注目的发现是 hsa-miR-132-3p（p = 6.37×10 ）、hsa-miR-497-5p（p = 1.35×10 ）和 hsa-miR-133b（p = 1.90×10 ）在大脑中，以及 hsa-miR-221-3p（p = 4.49×10 ）、hsa-miR-214-3p（p = 2.00×10 ）和 hsa-miR-29c-3p（p = 3.00×10 ）在血液中。CSF 中未发现显著信号。对大脑 miRNA 靶基因的全基因组关联研究数据的分析显示，九个基因座中的遗传变异与九个基因座显著相关（α = 9.40×10 ）。