Heterogeneity among patients with Parkinson's disease: cluster analysis and genetic association.

The clinical heterogeneity of Parkinson's disease (PD) reveals the presence of several PD subtypes. The objectives of this study were to identify PD subtypes using cluster analysis (CA) and to determine the association between the subtypes and the polymorphisms in LRRK2 (G2385R and R1628P) and GBA (L444P) genes. A k-means CA of demographics, disease progression, motor and non-motor symptoms was performed from 1,510 Chinese PD patients from the Chinese National Consortium on Neurodegenerative Diseases. Pearson correlation analysis was performed to eliminate uninformative characteristics. Blood samples from 852 patients were obtained for genetic analysis of LRRK2 and GBA. Genotypic associations between various subtypes and genetic variants were examined using chi-square test. We identified four different subtypes: subtype 1 was non-tremor dominant (NTD, n=469; 31.1%); subtype 2 had a rapid disease progression with late onset (RDP-LO, n=67; 4.4%); subtype 3 had benign pure motor characteristics (BPM, n=778; 51.5%) without non-motor disturbances; and subtype 4 was tremor dominant with slow disease progression (TD-SP, n=196; 13.0%). Subtypes 1, 2, and 4 had similar mean age of onset. No associations were identified between polymorphisms in LRRK2 (R1628P) and GBA (L444P) genes and the four subtypes (P>0.05).