Blood and brain tissue RNA transcriptomics reveal six potential targets of Parkinson's disease: a meta-analysis

The multi-factorial Parkinson's disease (PD) remains an incurable disease to date. Significant efforts have gone into identifying PD targets through high-throughput screening technologies such as microarrays and RNA sequencing. However, many studies often have low sample counts due to difficulty in obtaining human tissues, especially in neurodegenerative diseases, resulting in insufficient sample sizes for good statistical analysis. In this meta-analysis, we analysed 47 human blood and brain PD-associated datasets to identify clinically significant targets in PD. Our study excluded datasets with animal/in vitro models to eliminate species effects and in vitro artifacts.

To analyse all eligible human blood and brain PD-associated datasets available on Gene Expression Omnibus (GEO), including both microarrays and RNA-sequencing datasets, to provide a more comprehensive understanding of the clinically significant targets in PD.

Differentially expressed gene (DEG) and gene ontology analyses of 1922 human tissues samples identified 19 potential targets (13 in blood, 6 in brain) that were not previously PD-associated. DEGs involved in immune regulation in the blood, and apoptosis and cell growth/proliferation in the brain were consistently identified across multiple PD datasets. Separate cell type/tissue region analyses for both blood (leukocytes and PBMCs) and brain datasets (7 different regions) revealed more functionally-specific potential targets of PD. Via Cohen's d effect size, RNA-sequencing datasets display lower variability as compared to microarray datasets (p < 0.01). Separate region analysis also reduced data variability (p < 0.01). This is the largest human tissue meta-analysis conducted for PD to date. Importantly, we identified six significant DEGs dysregulated in the same direction in both the blood and brain of PD patients. Examining the roles of these targets in PD could advance our understanding of the disease in hopes of developing a neuroprotective treatment and/or early diagnostic biomarkers.