Objective: To systematically review recent advances in the genetics of Parkinson’s disease (PD), focusing on the mechanisms of major causal genes and biological insights derived from genome-wide association studies (GWAS), and to explore the clinical applications of genetic discoveries.

Background: PD is a complex neurodegenerative disorder resulting from interactions between genetic and environmental factors. Family-based studies have identified rare variants in over 30 genes that cause monogenic PD, while GWAS have identified more than 100 common loci associated with disease susceptibility. Despite these advances, a central challenge remains: how to integrate genetic data, from single gene mutations to polygenic risk scores, into comprehensive disease models to support clinical translation.

Method: This review synthesizes findings from family-based studies and GWAS, highlighting key pathogenic pathways, including mitochondrial dysfunction, vesicular transport impairment, and immune dysregulation. It further evaluates the potential and limitations of polygenic risk scores in risk stratification and preventive strategies, and highlights the integration of multi-modal data as a critical step toward precision medicine.

Results: Studies of highly penetrant causal genes have elucidated several key pathogenic pathways, including mitochondrial and vesicular transport dysfunction. In parallel, investigations of common risk loci have significantly advanced understanding of the genetic architecture of PD and implicated additional biological pathways, such as immune regulation. Polygenic risk scores show potential for risk stratification but face limitations in clinical utility.

Conclusion: he integration of multi-modal genetic data represents a critical step toward advancing precision medicine in PD. Further research is needed to translate genetic discoveries into comprehensive disease models and clinical applications.

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