Henderson Adrienne R, Wang Qi, Meechoovet Bessie, Siniard Ashley L, Naymik Marcus, De Both Matthew, Huentelman Matthew J, Caselli Richard J, Driver-Dunckley Erika, Dunckley Travis
Neurodegenerative Disease Research Center, Biodesign Institute, Arizona State University, Tempe, AZ, United States.
Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, United States.
Front Genet. 2021 Apr 26;12:640266. doi: 10.3389/fgene.2021.640266. eCollection 2021.
Parkinson's disease (PD) is the second most common age-related neurodegenerative disease. It is presently only accurately diagnosed at an advanced stage by a series of motor deficits, which are predated by a litany of non-motor symptoms manifesting over years or decades. Aberrant epigenetic modifications exist across a range of diseases and are non-invasively detectable in blood as potential markers of disease. We performed comparative analyses of the methylome and transcriptome in blood from PD patients and matched controls. Our aim was to characterize DNA methylation and gene expression patterns in whole blood from PD patients as a foundational step toward the future goal of identifying molecular markers that could predict, accurately diagnose, or track the progression of PD. We found that differentially expressed genes (DEGs) were involved in the processes of transcription and mitochondrial function and that PD methylation profiles were readily distinguishable from healthy controls, even in whole-blood DNA samples. Differentially methylated regions (DMRs) were functionally varied, including near transcription factor nuclear transcription factor Y subunit alpha (), receptor tyrosine kinase , RING finger ubiquitin ligase (), acetyltransferase , and vault RNA . Expression quantitative trait methylation sites were found at long non-coding RNA and transcription regulator among others. Functional epigenetic modules were highlighted by , , and . We identified patterns of altered disease-specific DNA methylation and associated gene expression in whole blood. Our combined analyses extended what we learned from the DEG or DMR results alone. These studies provide a foundation to support the characterization of larger sample cohorts, with the goal of building a thorough, accurate, and non-invasive molecular PD biomarker.
帕金森病（PD）是第二常见的与年龄相关的神经退行性疾病。目前，它仅在晚期通过一系列运动缺陷才能准确诊断，而在出现这些运动缺陷之前，会有一系列非运动症状在数年或数十年间显现出来。异常的表观遗传修饰存在于多种疾病中，并且可以在血液中通过非侵入性检测作为疾病的潜在标志物。我们对帕金森病患者和匹配的对照者血液中的甲基化组和转录组进行了比较分析。我们的目的是表征帕金森病患者全血中的DNA甲基化和基因表达模式，作为朝着识别可预测、准确诊断或追踪帕金森病进展的分子标志物这一未来目标迈出的基础步骤。我们发现，差异表达基因（DEGs）参与转录和线粒体功能过程，并且即使在全血DNA样本中，帕金森病的甲基化谱也很容易与健康对照区分开来。差异甲基化区域（DMRs）在功能上各不相同，包括靠近转录因子核转录因子Y亚基α（）、受体酪氨酸激酶、环状泛素连接酶（）、乙酰转移酶和穹窿体RNA 附近。在长链非编码RNA 和转录调节因子 等中发现了表达数量性状甲基化位点。功能表观遗传模块通过 、 和 得以突出显示。我们在全血中确定了疾病特异性DNA甲基化改变和相关基因表达的模式。我们的综合分析扩展了仅从DEG或DMR结果中学到的内容。这些研究为支持对更大样本队列的表征奠定了基础，目标是建立一个全面、准确且非侵入性的帕金森病分子生物标志物。
