Objective: To assess the distribution of genomic ancestries and rates of positive genetic findings in individuals enrolled in a large-scale return of results study for Parkinson’s disease (PD).

Background: PD GENEration (NCT04994015), sponsored by the Parkinson’s Foundation with support of the Global Parkinson’s Genetics Program (GP2), has enrolled >22,000 participants across the Americas and Israel. Although self-reported clinical data is captured, follow up genomic analyses have allowed for assessment of participant genomic ancestry.

Method: After targeted exome sequencing to capture pathogenic variants in seven PD genes, select participant DNA samples were sent to GP2 for further analysis and biobanking. Samples were assessed with the genome-wide Illumina NeuroBooster Array, which captures millions of variants, including >95,000 associated with neurological conditions. Statistical analysis of variant distribution was used to determine individual genomic ancestries. Here, we compare the genomic ancestries of participants to the self-reported race and ethnicity data captured upon enrollment and determine whether rates of disease-relevant variation differ between ancestral populations.

Results: To date, the Illumina Neurobooster Array has been performed on 6035 PD GENEration participants. Unsurprisingly, the largest proportion of participants are of European ancestry (75.8%). However, we identified multiple sources of potential discordance between genomic ancestry and self-reported race or ethnicity throughout the dataset. For example, of the 681 individuals that identify as Hispanic/Latino, 22.8% were of European genomic ancestry and 2.2% were of Ashkenazi Jewish genomic ancestry. This may have implications for their likelihood of carrying genetic risk factors for PD. In agreement with the literature, we found individuals with Ashkenazi Jewish ancestry had higher rates of GBA1 and LRRK2 variants than individuals from other populations.

Conclusion: Our results validate the need for genomic ancestral analysis in large-scale genetic studies of PD to accurately assess disease risk across populations. The high proportion of individuals of European ancestry in PD GENEration has driven efforts to prioritize greater ancestral diversity in recruitment to better capture genetic variation related to disease risk.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/distribution-of-genomic-ancestries-and-genetic-variation-among-individuals-enrolled-in-the-pd-generation-study/