Introduction: Parkinson’s disease (PD) is a common neurodegenerative movement disorder characterized by motor features and a range of non-motor manifestations that vary substantially across those affected. PD has a complex, multifactorial etiology arising from interactions between environmental exposures and genetic susceptibility. Accumulating evidence from candidate gene studies and genome-wide associations studies suggest that genetic variation not only influences disease risk but also may explain some of the observed clinical variability. Accordingly, this systematic review synthesizes current evidence on genotype-phenotype associations in PD to examine the strength and the consistency of the evidence for genetic contributions to PD clinical manifestations, and also to identify biological pathways underlying this clinical variability. Methods: Following PRISMA guidelines, MEDLINE and Embase were searched for human genetic association studies investigating genotype-phenotype associations in PD. Functional enrichment analyses identified overrepresented biological processes across implicated genes. Results: We identified 5,734 publications, of which 33 met inclusion criteria. Genetic influences on the clinical manifestations of PD have been investigated predominantly through genes implicated in monogenic forms, with GBA and LRRK2 emerging as the most frequently studied. GBA variants consistently correlated with earlier onset, hyposmia, autonomic dysfunction, cognitive decline, and greater non-motor symptom burden. LRRK2 variants were linked to later onset, relatively preserved olfaction, and milder non-motor features. Functional enrichment analyses revealed distinct biological patterns. Genes associated with age at onset were enriched for neuronal maintenance and degeneration, those linked to olfactory function in autonomic and gliotic processes, genes related to non-motor symptoms in dopaminergic and catecholamine signaling, those associated with motor signs in synaptic transmission, oxidative stress, and clinical features of PD, and genes linked to disease severity in cellular stress and protein stability. Conclusions: Distinct genetic variants appear to contribute to specific clinical manifestations of PD, and pathway-level enrichment analyses generate hypotheses about the partially distinct biological processes that may be involved. These findings highlight the need for integrative genomic and longitudinal research to refine patient stratification and guide personalized therapeutic strategies.