Large cross-sectional cohort of 10,929 Australians with Parkinson's characterizing demographics, environmental exposures, comorbidities, and sex differences with planned genomic and digital phenotyping.

Establishes a powerful, scalable resource for genetic analyses, risk stratification, biomarker discovery, and sex-specific research that can enable target identification and therapeutic cohort recruitment, though its cross-sectional, self-reported design limits immediate mechanistic or…

BACKGROUND: The pathogenesis of Parkinson's disease (PD) remains incompletely understood; large-scale studies are needed to further elucidate its genetic and environmental underpinnings. The Australian Parkinson's Genetics Study (APGS) is an ongoing nationwide, population-based initiative established to advance understanding of PD determinants and progression. METHODS: We present a cross-sectional characterisation of 10,929 participants with self-reported PD recruited across Australia through assisted mail-outs, media outreach, and digital engagement. Participants complete comprehensive questionnaires capturing sociodemographic, clinical, environmental, lifestyle, and behavioural data, and provide saliva samples for genetic analysis. A control cohort is currently being recruited and not reported here. FINDINGS: The cohort is 63% male, with a mean age of 71 years and symptom onset at 64 years; 79% report diagnosis by a neurologist and 25% report a family history. Non-motor symptoms and neuropsychiatric comorbidities are common, including sleep disturbances, memory changes, and depression, alongside risk factors such as pesticide exposure (36%), traumatic brain injury (16%), and high-risk occupations (33%). Sex-based differences are evident: females more frequently report unilateral onset (81% vs 75%), falls (45% vs 41%), and pain (70% vs 63%), whereas males report higher rates of memory changes (67% vs 61%), pesticide exposure (42% vs 28%), high-risk occupations (44% vs 16%), and impulsive control behaviour, such as sexual behaviour (56% vs 19%). INTERPRETATION: Leveraging APGS, the largest active PD cohort globally, our findings highlight the clinical and risk heterogeneity of PD and the importance of sex-specific research and care. The study's successful recruitment demonstrates the feasibility of large-scale remote enrolment, while its comprehensive design and ongoing expansion, including genomic profiling and digital phenotyping, position APGS as a transformative platform for advancing PD risk prediction, biomarker discovery, and therapeutic development. FUNDING: APGS is supported by the Global Parkinson's Genetics Program (GP2), Shake It Up Australia Foundation, and Michael J. Fox Foundation for Parkinson's Research (MJFF-021952).