To identify circRNAs associated with Parkinson’s disease (PD) we leveraged two of the largest publicly available studies with longitudinal clinical and blood transcriptomic data. We performed a cross-sectional study utilizing the last visit of each participant (N = 1848), and a longitudinal analysis that included 1166 participants with at least two time points. We identified 192 differentially expressed circRNAs, with effects that were sustained during disease, in mutation carriers, and diverse ancestry. The 192 circRNAs were leveraged to distinguish between PD and healthy participants with a ROC AUC of 0.797. Further, 71 circRNAs were sufficient to distinguish between genetic PD (AUC₇₁ = 0.954) and, at-risk participants (AUC₇₁ = 0.929) and healthy controls, supporting that circRNAs have the potential to aid the diagnosis of PD. Finally, we identified five circRNAs highly correlated with symptom severity. Overall, we demonstrated that circRNAs play an important role in PD and can be clinically relevant to improve diagnostic and monitoring.

为了鉴定与帕金森病 （PD） 相关的 circRNA，我们利用了两项最大的公开研究，其中包含纵向临床和血液转录组学数据。我们利用每位参与者的最后一次就诊 （N = 1848） 进行了一项横断面研究，并进行了一项纵向分析，该分析包括 1166 名参与者，至少有两个时间点。我们鉴定了 192 个差异表达的 circRNA，这些 RNAs 在疾病期间、突变携带者和不同祖先中具有持续的影响。利用 192 个 circRNAs 来区分 PD 和健康参与者，ROC AUC 为 0.797。此外，71 个 circRNA 足以区分遗传性 PD （AUC₇₁ = 0.954） 和高危参与者 （AUC₇₁ = 0.929） 和健康对照，支持 circRNA 有可能帮助诊断 PD。最后，我们确定了 5 个与症状严重程度高度相关的 circRNA。总体而言，我们证明 circRNAs 在 PD 中起重要作用，并且可能与改善诊断和监测具有临床相关性。