Beric Aleksandra, Sun Yichen, Sanchez Santiago, Martin Charissa, Powell Tyler, Kumar Ravindra, Pardo Jose Adrian, Darekar Gauri, Sanford Jessie, Dikec Devin, Phillips Bridget, Botia Juan A, Cruchaga Carlos, Ibanez Laura
Department of Psychiatry, Washington University in Saint Louis School of Medicine, St. Louis, MO, USA.
NeuroGenomics and Informatics Center, Washington University in Saint Louis School of Medicine, St. Louis, MO, USA.
NPJ Parkinsons Dis. 2024 Nov 18;10(1):222. doi: 10.1038/s41531-024-00839-3.
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 (AUC = 0.954) and, at-risk participants (AUC = 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）相关的环状RNA（circRNA），我们利用了两项最大的公开可用研究，这些研究包含纵向临床和血液转录组数据。我们进行了一项横断面研究，利用了每个参与者的最后一次随访（N = 1848），以及一项纵向分析，该分析纳入了1166名至少有两个时间点的参与者。我们鉴定出192种差异表达的circRNA，其影响在疾病期间、突变携带者以及不同血统中持续存在。利用这192种circRNA区分PD患者和健康参与者，受试者工作特征曲线下面积（ROC AUC）为0.797。此外，71种circRNA足以区分遗传性PD（AUC = 0.954）、高危参与者（AUC = 0.929）和健康对照，这支持了circRNA有潜力辅助PD的诊断。最后，我们鉴定出5种与症状严重程度高度相关的circRNA。总体而言，我们证明了circRNA在PD中起重要作用，并且在临床上可能与改善诊断和监测相关。
