Objective: To continue recruitment of global ‘at-risk’, early and prodromal Parkinson’s disease (PD) cohorts to the Global Parkinson’s Genetics Program (GP2, http://gp2.org/), support existing cohorts to expand their clinico-genetic data collection and continue our contribution to GP2’s global resource for studying prodromal PD.

Background: GP2 is an international collaborative project to accelerate research into the genetic architecture of PD. Alongside developing a global network for researchers and trainees, GP2 aims to harmonise clinical and genetic data for >300,000 participants worldwide. The prodromal effort in GP2 began in 2023 with the goal of capturing individuals ‘at-risk’ or in the earliest prodromal stages of PD. This effort aims to continue gathering data from individuals with prodromal PD and support existing cohorts to expand their collection.

Method: GP2’s prodromal recruitment focuses on individuals with known early features of PD (Rapid Eye Movement [REM] sleep behaviour disorder [RBD], olfactory dysfunction, and pure autonomic failure [PAF]), genetic risk factors (carriers of rare pathogenic or risk-associated GBA1 or LRRK2 variants or individuals with a high polygenic risk score), or those scoring highly on PD risk algorithms (MDS criteria or PREDICT-PD algorithm). We prioritise polysomnography (PSG)-confirmed RBD, clinically confirmed anosmia, hyposmia defined by objective smell tests, and non-manifesting GBA1/LRRK2 variant carriers. We encourage cohorts already enrolled in GP2, particularly those from underrepresented populations, to consider supported expansion by contributing extended clinical data, training staff in new data collection methods (like PSG) or undertaking new sample drives.

Results: Since 2023, we have engaged with >160 cohorts. Sixteen cohorts have sent samples for genotyping, contributing 5260 prodromal samples to the GP2 database, of whom 4241 have extended clinical data. We anticipate that >18,500 cohort-estimated prodromal samples will be available by the end of 2029, forming one of the largest open access genetic and clinical datasets for prodromal PD.

Conclusion: The GP2 prodromal effort has continued to expand since its conception, contributing >5000 samples to the GP2 network to date. We are particularly interested in engaging with new investigators to set up prodromal collections in under-represented populations.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/understanding-the-earliest-phases-of-parkinsons-disease-an-update-on-the-prodromal-effort-within-the-global-parkinsons-genetics-program/