Objective: To address the pressing need through promoting collaborative translational work evaluating genetic signatures in Latinx and African-American (AA) participants with and without Parkinson’s disease (PD) in the BioMe biobank.

Background: Genetic studies have facilitated understanding pathophysiology and identification of pharmacologic targets and biomarkers in PD; however, neither LRRK2 nor GBA has been well-studied in AA and Latinx populations, and even among genetic databases. BioMe data is comprised of electronic health record (EHR)-linked bio and data that non-selectively enrolls individuals from Mount Sinai sites in Manhattan, Brooklyn, Queens and the Bronx. With over 60,000 participants, BioMe is the largest, most diverse cohort ever ascertained at a single urban medical center under uniform study protocol and consent procedures. Importantly, the BioMe cohort is ethnically/racially diverse, with 35% Hispanic/Latino, 24% African, and 32% European ancestry.

Method: The BioMe data will be extensively interrogated (1) to determine frequency and phenotypes of major and previously reported LRRK2 and GBA variants in LatinX and AA parkinsonism through rigorous chart review of clinical features and using self-reported ethnicity and genetically-determined ancestry, as well as (2) to better understand genetic architecture of the two top susceptibility genes for PD using whole exome sequencing data in Latinx and AA PD cases and matched controls.

Results: As preliminary analysis, we have observed an increase in the LRRK2 p.Gly2019Ser carriers (42/21,240) in the BioMe dataset when compared to the GnomAD dataset (9/35,406) among Hispanics/Latinx population (Fisher’s exact, p<0.01), while similar frequencies were observed in both datasets among AA (1/14,823 (BioMe) vs 3/24,962; p=1.0). Higher frequencies were also observed in the BioMe dataset for the GBA p.Asn409Ser variant in the Hispanic population (32/21,240 vs 27/35,432; p<0.01), but not among AAs (4/14,834 vs 5/24,592; p=0.449).

Conclusion: We demonstrated that there are carriers of the LRRK2 p.Gly2019Ser and GBA p.Asn409Ser variants in both New York Hispanic and AA populations. We expect that greater frequency of mutation carriers in the BioMe samples is attributable to a higher number of PD patients in the BioMe dataset. This will be better determined by linking to case diagnosis which is underway.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/investigating-lrrk2-and-gba-genetic-variability-in-underrepresented-populations/