Altered ubiquitin signaling and disrupted protein quality control have been implicated in the pathogenesis of PD. The aim of the study was to systematically examine the overlaps between E3 ubiquitin ligase genes and early onset PD (EOPD). A total of 695 EOPD patients were analyzed aggregate burden for rare variants (MAF <0.001 and MAF <0.0001) in a total of 44 E3 ubiquitin ligase genes causing disorders involved in the nervous system. There was significant enrichment of the rare and rare damaging variants in the E3 ubiquitin ligase genes in EOPD patients. Detailly, in the gene-based level, the strongest associations were found in HERC1, IRF2BPL, KMT2D, RAPSN, RLIM, RNF168 and RNF216. Our findings highlighted the importance of UPS mechanism in the pathogenesis of PD from the genetic perspective. Moreover, our study also expanded the susceptible gene spectrum for PD.

改变的泛素信号传导和破坏的蛋白质质量控​​制与 PD 的发病机制有关。该研究的目的是系统地检查 E3 泛素连接酶基因与早发性 PD (EOPD) 之间的重叠。在总共 44 个 E3 泛素连接酶基因中分析了 695 名 EOPD 患者的罕见变异（MAF <0.001 和 MAF <0.0001）的总负担，这些基因导致神经系统疾病。EOPD 患者的 E3 泛素连接酶基因中罕见和罕见的破坏性变异显着富集。详细地说，在基于基因的水平上，最强的关联出现在HERC1、IRF2BPL、KMT2D、RAPSN、RLIM、RNF168和RNF216。我们的研究结果从遗传角度强调了 UPS 机制在 PD 发病机制中的重要性。此外，我们的研究还扩大了 PD 的易感基因谱。