Introduction: Parkinson’s disease (PD) is caused by the interplay of genetic and environmental factors during brain aging. About 90 single nucleotide polymorphisms (SNPs) have been recently discovered associations with PD, but whether they associate with the clinical features of PD have not been fully addressed yet. Methods: Clinical data of 365 patients with PD who enrolled in Parkinson’s Progression Markers Initiative (PPMI) study were obtained. Patients with rapid motor progression were determined through clinical assessments over five years follow-up. In addition, genetic information of 44 targeted SNPs was extracted from the genetic database of NeuroX for the same cohort. Logistic regression was used to analyze the genetic associations with rapid motor progression of PD. Results: Among 365 patients with PD, there are more male (66%) than female (34%). Seven SNPs (rs6808178, rs115185635, rs12497850, rs34311866, rs3793947, rs11060180, rs9568188) were associated with faster motor progression (p 0.05), and only rs6808178 passed multiple comparison correction (p 0.0011). In addition, the extended 44 SNPs with autonomic dysfunction reach a fair prediction of AUC at 0.821. Conclusion: Genetics and autonomic function factors contribute to the motor progression at the clinical initiation of PD.