ObjectiveParkinson's disease (PD) and dystonia are two closely related movement disorders with overlaps in clinical phenotype. Variants in several dystonia-related genes were demonstrated to be associated with PD; however, genetic evidence for the involvement of dystonia-related genes in PD has not been fully studied. Here, we comprehensively investigated the association between rare variants in dystonia-related genes and PD in a large Chinese cohort.MethodsWe comprehensively analyzed the rare variants of 47 known dystonia-related genes by mining the whole-exome sequencing (WES) and whole-genome sequencing (WGS) data from 3,959 PD patients and 2,931 healthy controls. We initially identified potentially pathogenic variants of dystonia-related genes in patients with PD based on different inheritance models. Sequence kernel association tests were conducted in the next step to detect the association between the burden of rare variants and the risk for PD.ResultsWe found that five patients with PD carried potentially pathogenic biallelic variants in recessive dystonia-related genes includingCOL6A3andTH. Additionally, we identified 180 deleterious variants in dominant dystonia-related genes based on computational pathogenicity predictions and four of which were considered as potentially pathogenic variants (p.W591X and p.G820S inANO3, p.R678H inADCY5, and p.R458Q inSLC2A1). A gene-based burden analysis revealed the increased burden of variant subgroups ofTH, SQSTM1, THAP1, andADCY5in sporadic early-onset PD, whereasCOL6A3was associated with sporadic late-onset PD. However, none of them reached statistical significance after the Bonferroni correction.ConclusionOur findings indicated that rare variants in several dystonia-related genes are suggestively associated with PD, and taken together, the role ofCOL6A3andTHgenes in PD is highlighted.