Circulating blood circular RNA in Parkinson's Disease; a systematic study

Abstract

We aimed to identify circRNAs associated with Parkinson's disease (PD) by leveraging 1,848 participants and 1,789 circRNA from two of the largest publicly available studies with longitudinal clinical and blood transcriptomic data. To comprehensively understand changes in circRNAs we performed a cross-sectional study utilizing the last visit of each participant, and a longitudinal (mix model) analysis that included 1,166 participants with at least two time points. We identified 192 circRNAs differentially expressed in PD participants compared to healthy controls, with effects that were consistent in the mixed models, mutation carriers, and diverse ancestry. Finally, we included the 149 circRNA in a model with a ROC AUC of 0.825, showing that have the potential to aid the diagnosis of PD. Overall, we demonstrated that circRNAs play an important role in PD and can be leveraged as biomarkers.

Figure1.

Study design summary. We have followed a two-stage cross-sectional analysis with discovery (PDBP) and replication (PPMI) phases. Then we have performed sensitivity analysis for the top hits by approaching the analysis in a longitudinal manner (Mixed model), stratifying by mutation, exploring individuals from African Ancestry, and those at risk due to being a carrier of a PD -causing mutation, or suffering from RBD or hyposmia. Finally, we have performed functional annotation via circRNA -miRNA integration and leveraged th e circRNA to build predictive models.

Figure2.

Results of the cross sectional analysis; A. Volcano plot showing circRNAs that are differentially expressed in the PDBP dataset, with replicated circRNAs in PPMI labeled; B. Summary results of the main findings including sensitivity analyses