Introduction Genetic factors play an important role in Parkinson's disease (PD) risk. However, the genetic contribution to progression in Chinese PD patients has rarely been studied. This study investigated genetic associations with progression based on 30 PD risk loci common in a longitudinal cohort of Chinese PD patients and the Parkinson's Progression Markers Initiative (PPMI) cohort. Methods PD patients from the true world (TW) Chinese PD longitudinal cohort and the PPMI cohort with demographic information and assessment scales were assessed. A panel containing 30 PD risk single nucleotide polymorphisms was tested. Progression rates of each scale were derived from random-effect slope values of mixed-effects regression models. Progression rates of multiple assessments were combined by using principal component analysis (PCA) to derive scores for composite, motor, and nonmotor progression. The association of genetic polymorphism and separate scales or PCA progression was analysed via linear regression. Results In the Chinese PD cohort, MAOB rs1799836 was associated with progression based on the Montreal Cognitive Assessment, the top 3 principal components (PCs) of nonmotor PCA and PC1 of the composite PCA. In the PPMI cohort, both MDS-Unified Parkinson's Disease Rating Scale II and motor PC1 progression were associated with RIT2 rs12456492. The PARK16 haplotype was associated with Geriatric Depression Scale and the State-Trait Anxiety Inventory for Adults progression, and the SNCA haplotype was associated with the Hoehn-Yahr staging progression and motor PC1 progression. Ethnicity-stratified analysis showed that the association between MAOB rs1799836 and PD progression may be specific to Asian or Chinese patients. Conclusion MAOB rs1799836 was associated with the progression of nonmotor symptoms, especially cognitive impairment, and the composite progression of motor and nonmotor symptoms within our Chinese PD cohort. The RIT2 rs12456492 and SNCA haplotypes were associated with motor function decline, and the PARK16 haplotype was associated with progression in mood in the PPMI cohort.

Background Differences between male and female have been studied for PD but limited data was focused on the comparison between sexes with LRRK2 G2385 variant. Objective This study was to explore sex effects in the same genetic subtype and role of leucine-rich repeat kinase 2 (LRRK2) G2385R variants in the same sex. Methods 613 PD Patients were recruitment from Movement Disorders Clinic in Ruijin Hospital. Clinical data including demographic information, disease history, scales of motor and non-motor symptoms, midbrain transcranial sonography and DNA was collected. Binary logistic regression analysis was performed to evaluate the possible association between the clinical features and sex in LRRK2 G2385R carriers and non-carriers, and to evaluate the possible association between the clinical features and LRRK2 G2385R variants in male and female. Results Sex distribution is similar in LRRK2 G2385R carriers and non-carriers. In male sex, LRRK2 G2385R carriers showed lower risk in cognitive impairment compared with non-carriers (OR = 0.301, p = 0.003, 95%CI 0.135–0.668). In female sex, LRRK2 G2385R carriers showed lower risk in autonomic dysfunction compared with non-carrier (OR = 0.401, p = 0.040, 95%CI 0.167–0.960). In LRRK2 G2385R non-carriers, female showed lower risk of impairment in activity of daily living (OR = 0.610, P = 0.021, 95%CI 0.400-0.928), excessive daytime sleepiness (OR = 0.555, p = 0.007, 95%CI 0.361–0.853), substantia nigra hyperechogenicity (OR = 0.448, P = 0.019, 95%CI 0.228–0.878), autonomic dysfunction frequency (OR = 0.626, p = 0.016, 95%CI 0.428–0.917) and higher risk in mood disorders (OR = 1.691, p = 0.022, 95%CI (1.078–2.654) compared with male. In LRRK2 G2385R carriers, female showed a lower risk of autonomic dysfunction (OR = 0.294, p = 0.024, 95%CI 0.102–0.849) compared with male. Conclusion A more benign disease course was observed in female compared to male in both LRRK2 G2385R carriers and non-carriers. However, sex differences were less notable in PD with LRRK2 carriers.