Objective: This study evaluates the shift from Euro-centric data to a diversified landscape. We aim to quantify the performance of European-derived Polygenic Risk Scores (PRS) in African cohorts and identify population-specific risk variants through the GP2 framework.

Background: Parkinson’s disease (PD) is the world’s fastest-growing neurodegenerative disorder, with significant prevalence surges projected for Africa by 2030. Historically, 90% of PD genetic research has centered on European populations, creating a “genomic gap” that limits the global efficacy of precision medicine and diagnostic tools.

Method: Utilizing the NeuroBooster Array (NBA)—a tool designed for 11 distinct ancestries—and the Terra cloud platform, we analyzed trans-ancestry meta-GWAS data. The study prioritized 134 independent risk loci, focusing on local ancestry deconvolution and functional multi-omics to identify high-confidence genes.

Results: Data from 2025 reveals that while traditional PRS achieve an AUC of 0.70 in European cohorts, accuracy drops to 0.58–0.63 in African and Admixed populations without refinement. However, the identification of 59 novel loci, including African-specific GBA1 variants and the p.Leu444Pro mutation, has enabled the nomination of 33 genes for therapeutic follow-up.

Conclusion: The transition toward ancestry-aware risk assessment is uncovering critical pathways, such as lysosomal dysfunction, previously obscured by a “one-size-fits-all” model. For regions like Nigeria, integrating these local genetic insights with affordable clinical technologies is essential to mitigate the global burden of PD and ensure equitable access to future neuroprotective therapies.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/bridging-the-genomic-gap-ancestry-aware-polygenic-risk-and-variant-discovery-in-african-parkinsons-disease-cohorts/