Research Article Bioinformatic Analysis of Genetic Factors from Human Blood Samples and Postmortem Brains in Parkinson’s Disease Longping Yao , 1 Kai Lin, 2 Zijian Zheng, 3 Sumeyye Koc, 4 Shizhong Zhang, 5 Guohui Lu , 3 and Thomas Skutella 1 1 Department of Neuroanatomy, Group for Regeneration and Reprogramming, Institute for Anatomy and Cell Biology, Medical Faculty, Heidelberg University, 69120 Heidelberg, Germany 2 Nursing Department of Zengcheng Branch, Nanfang Hospital, No. 28 Innovation Avenue, Zengcheng, Guangzhou 511300, China 3 Department of Neurosurgery, First Affiliated Hospital of Nanchang University, 330006 Nanchang, China 4 Department of Neuroscience, Institute of Health Sciences, Ondokuz Mayıs University, 55200 Samsun, Turkey 5 Department of Neurosurgery, Southern Medical University, 510280 Guangzhou, China Correspondence should be addressed to Guohui Lu; guohui-lu@163.com and Thomas Skutella; thomas.skutella@uni-heidelberg.de Received 19 October 2022; Revised 8 December 2022; Accepted 9 December 2022; Published 24 December 2022 Academic Editor: Sachchida Nand Rai Copyright © 2022 Longping Yao et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Parkinson’s disease (PD) is one of the most prevalent neurodegenerative disorders characterized by motor and nonmotor symptoms due to the selective loss of midbrain dopaminergic neurons. Pharmacological and surgical interventions have not been possible to cure PD; however, the cause of neurodegeneration remains unclear. Here, we performed and tested a multitiered bioinformatic analysis using the GEO and Proteinexchange database to investigate the gene expression involved in the pathogenesis of PD. Then we further validated individual differences in gene expression in whole blood samples that we collected in the clinic. We also made an interaction analysis and prediction for these genetic factors. There were in all 1045 genes expressing differently in PD compared with the healthy control group. Protein-protein interaction (PPI) networks showed 10 top hub genes: ACO2, MDH2, SDHA, ATP5A1, UQCRC2, PDHB, SUCLG1, NDUFS3, UQCRC1, and ATP5C1. We validated the ten hub gene expression in clinical PD patients and showed the expression of MDH2 was significantly different compared with healthy control. Besides, we also identified the expression of G6PD, GRID2, RIPK2, CUL4B, BCL6, MRPS31, GPI, and MAP 2 K1 were all significantly increased, and levels of MAPK, ELAVL1, RAB14, KLF9, ARF1, ARFGAP1, ATG7, ABCA7, SFT2D2, E2F2, MAPK7, and UHRF1 were all significantly decreased in PD. Among them, to our knowledge, we presently have the most recent and conclusive evidence that GRID2, RIPK2, CUL4B, E2F2, and ABCA7 are possible PD indicators. We confirmed several genetic factors which may be involved in the pathogenesis of PD. They could be promising markers for discriminating the PD and potential factors that may affect PD development. 1. Introduction Parkinson’s disease (PD) is an age-related progressive neu- rodegenerative disorder caused by selective loss of midbrain dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) [1–5]. It has been a worldwide public health problem characterized by motor and nonmotor symptoms [6, 7]. Lewy bodies, protein aggregates containing α-synuclein, are often deposited in several brain areas of people with PD [8]. Motor symptoms, primarily dependent on dopaminergic nigrostriatal denervation, gradually mani- fest as DA neuron survival decreases [1]. People with PD also have sleep issues, exhaustion, changed mood, cognitive problems, autonomic dysfunction, and pain as the illness progresses and neurodegeneration worsens [9]. These symp- toms result from alterations occurring at various levels of the brain. The primary pathogenic alteration is the gradual deg- radation of neurons in the substantia nigra pars compacta, one of the basal ganglia’s nuclei [10]. These neurons are involved in the transmission of dopamine to the striatum Hindawi Oxidative Medicine and Cellular Longevity Volume 2022, Article ID 9235358, 18 pages https://doi.org/10.1155/2022/9235358