Background: Recent studies have advanced our understanding of the genetic drivers of Parkinson's disease (PD). Rare variants in more than 20 genes are considered causal for PD, and the latest PD genome‐wide association study (GWAS) identified 90 independent risk loci. However, there remains a gap in our understanding of PD genetics outside of the European populations in which the vast majority of these studies were focused.Objective: The aim was to identify genetic risk factors for PD in a South Asian population.Methods: A total of 674 PD subjects predominantly with age of onset (AoO) ≤50 years (encompassing juvenile, young, or early‐onset PD) were recruited from 10 specialty movement disorder centers across India over a 2‐year period; 1376 control subjects were selected from the reference population GenomeAsia, Phase 2. We performed various case‐only and case–control genetic analyses for PD diagnosis and AoO.Results: A genome‐wide significant signal for PD diagnosis was identified in the SNCA region, strongly colocalizing with SNCA region signal from European PD GWAS. PD cases with pathogenic mutations in PD genes exhibited, on average, lower PD polygenic risk scores than PD cases lacking any PD gene mutations. Gene burden studies of rare, predicted deleterious variants identified BSN, encoding the presynaptic protein Bassoon that has been previously associated with neurodegenerative disease.Conclusions: This study constitutes the largest genetic investigation of PD in a South Asian population to date. Future work should seek to expand sample numbers in this population to enable improved statistical power to detect PD genes in this understudied group. © 2023 Denali Therapeutics and The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Background: During the past decade the view of Parkinson's disease (PD) as a motor disorder has changed significantly and currently it is recognized as a multisystem disorder with diverse non-motor symptoms (NMS). Aims: The present study aimed to evaluate and characterize the NMS and study their impact on quality of life (QoL) in a PD patient cohort. Material and Methods: This was a cross-sectional study where 92 PD patients fulfilling the UK Parkinson's disease society brain bank criteria were enrolled from a movement disorder clinic. All patients were evaluated using unified Parkinson's disease rating scale, non-motor symptoms scale (NMSS) for the non-motor symptoms, and Parkinson's disease questionnaire-39 (PDQ-39) for the QoL. The impact of NMS on QoL was assessed statistically. Results: A total of 92 patients were enrolled with a mean age of 55.40 ± 7.37 years, mean age of onset of disease 51.62 ± 6.38 years, and mean disease duration of 3.78 ± 1.54 years. Type of disease was akinetic rigid variant in 29.3% (n = 27), tremor predominant type in 36.9%(n = 34), and mixed type in 33.6% (n = 31). Mean Hoehn and Yahr stage was 2.12 ± 0.54. In the NMSS, most common symptom was sleep and fatigue (83%), followed by urinary tract symptoms (63%), mood and cognition (51%), cardiovascular symptoms and falls (43%), gastrointestinal tract symptoms (38%), and sexual function (33%). Univariate analyses showed that all NMS domains had a significant correlation with PDQ-39 with P < 001. Conclusion: Our study shows that NMS in PDare fairly common and significantly impact the QoL.

Background: Cognitive impairment is increasingly being recognized as a major cause of morbidity and increased dependence over the caregivers in Parkinson's disease (PD) patients. Objective: The present study aimed to compare the cognition testing in young- and late-onset PD patient. Methods: Sixty PD patients (20 young onset and 40 late onset) fulfilling UKPDS Brain Bank diagnostic criteria were enrolled in the study. Patients were assessed clinically and using scales for cognition testing such as Scales for Outcomes in PDCognition (SCOPA-COG), Unified Parkinson's Disease Rating scale (motor part), and Hoehn and Yahr staging. Results: Young-onset group comprised 20 (33.3%) and late-onset group comprised 40 (66.7%) patients. Most of the young- and late-onset patients, 15 (75%) and 21 (52.5%), had SCOPA-COG score in the range of 30–39, respectively. On comparison between young- and late-onset groups, SCOPA-COG score's mean ± standard deviation (SD) for young and late onset was 32.60 ± 2.52 and 30.30 ± 3.65, respectively, with statistical significance (P = 0.01). SCOPA-COG score's mean ± SD for mild, moderate, and severely impaired PD patients was 31.48 ± 3.19, 30.60 ± 3.24, and 23.50 ± 3.53, respectively, which on group comparisons (ANOVA) were statistically significant (P = 0.004). However, the SCOPA-COG score was statistically insignificant with respect to disease duration. Conclusion: There was statistically significant difference in SCOPA-COG score between young- and late-onset PD patients and in patients with more severe motor impairment.