Objective: To identify and recruit at-risk/early/prodromal Parkinson’s disease (PD) cohorts around the world to the Global Parkinson’s Genetics Program (GP2, http://gp2.org/) and build a global resource for studying the earliest phases of PD.

Background: GP2 is an international collaborative effort to accelerate research into the genetic basis of PD. Alongside developing a global network of researchers, GP2 aims to integrate clinical and genetic data from >200,000 participants. GP2 recently expanded to include individuals identified as being ‘at risk’ of or in an ‘early’ or ‘prodromal’ stage of PD. Understanding the genetic basis of the earliest phases of PD is crucial given the highly heterogeneous nature of PD. This expanding effort aims to gather clinico-genetic data from individuals with prodromal PD worldwide, making it a highly valuable resource for PD research.

Method: The prodromal effort includes individuals based on various models of prodromal PD, including groups that are ‘at risk’ by virtue of genetic risk factors (e.g. carriers of rare pathogenic variants in GBA1 or LRRK2, or high polygenic risk score [PRS]), a single indicative early clinical feature (e.g. REM sleep behavior disorder [RBD] or hyposmia), or combinations of risk factors used to stratify in population-based studies (e.g. MDS criteria or PREDICT-PD algorithm). To increase the likelihood of including true prodromal individuals, we are prioritizing polysomnography (PSG)-confirmed RBD, hyposmia confirmed by a smell clinic or defined by objective smell tests, and non-manifesting GBA1/LRRK2 variant carriers.

Results: We have engaged with >60 cohorts which account for over 7,852 prodromal samples. We are anticipating around 10,000 samples by the end of 2025, which will allow us to create one of the largest unified datasets for analyzing prodromal PD.

Conclusion: The prodromal effort in GP2 will generate an open access data analysis resource and bring together researchers worldwide studying ‘at-risk’/early/prodromal PD. Utilizing the pathways and protocol set up in GP2 will allow us to rapidly expand the resource, allowing vital studies of the earliest phases of the disease. We are interested in engaging with investigators who might be able to establish new prodromal collections in under-represented parts of the world, where we could support genotyping.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/understanding-the-earliest-phases-of-parkinsons-disease-pd-an-expanding-opportunity-to-study-at-risk-early-prodromal-pd-in-the-global-parkinsons-genetics-progra/