Genetic Associations and Functional Pathways in Parkinson's Disease: A Meta-Analytic Insight into LRRK2 Mutation Impact

Abstract

<title>Abstract</title> <bold>Background</bold>: Parkinson's Disease (PD) is a complex neurodegenerative disorder with elusive pathophysiological mechanisms. Recent studies have highlighted the role of genetic variations and metabolic changes in PD progression. <bold>Aim</bold>: This study aims to investigate the genetic disparities in PD, particularly focusing on LRRK2 mutations, and to analyze the associated metabolic pathway alterations. <bold>Methodology</bold>: The study utilized R programming with MetaIntegrator for meta-analysis and ggplot2 for visualization. Datasets underwent preprocessing, and the MetaIntegrator package computed meta scores, effects, and ROC analysis. Differential gene expression and functional enrichment analyses provided insights into genetic associations and pathways in Parkinson's disease and LRRK2 mutations. <bold>Results</bold>: Significant meta-score differences were observed in PD patients, especially in datasets GSE133347, GSE36321, and GSE100054, underscoring the impact of LRRK2 mutations. Genes like SKAP2 and IFNGR2 were significantly upregulated, implicating their role in neuroinflammation. Moreover, a shift in metabolic pathways, particularly carbohydrate kinase activity, was noted, indicating altered energy metabolism in PD cells. <bold>Conclusion:</bold> The study reinforces the genetic heterogeneity of PD and highlights the potential therapeutic importance of targeting neuroinflammatory pathways and metabolic dysfunctions. These findings suggest new avenues for diagnostic and therapeutic strategies in PD management.