Category: Parkinson's Disease: Genetics
Objective: To investigate the frequency of a newly proposed PD risk factor in an intronic region of GBA1 in people with PD from the PD GENEration study.
Background: Recently, a novel PD risk factor (rs3115534-G) in the 8th intron of GBA1 was found to be carried by ~50% of West African people living with PD (PwP)1. The variant results in the inclusion of intron 8 in the final transcript and causes reduced glucocerebrosidase (GCase) activity2. Here, we leverage whole genome sequencing (WGS) data from The PD GENEration study (NCT04994015), sponsored by the Parkinson’s Foundation with support of Aligning Science Across Parkinson’s through the Global Parkinson’s Genetics Program (GP2), to determine the prevalence of the risk allele in an international cohort of PwP.
Method: Participants enrolled in the WGS iteration of PD GENEration between March 2024 and January 2026 were included in the GBA1 intronic variant analyses. WGS was performed by Fulgent Genetics following established methodologies and quality control. WGS data were queried for the rs3115534-G variant. Only samples with a read depth >20X at the variant position were retained for analyses.
Results: We queried the WGS of 12,129 PD GENEration participants for the GBA1 variant rs3115534-G. Of these, 196 (1.6%) PwP were heterozygous carriers of the PD risk allele and 30 (0.3%) were homozygous carriers of the G risk allele. The largest proportion of these individuals had self-reported their race as Black/African American (n = 126, 55.8%). The carriers represented 43.4% of all participants that reported their race as Black/African American (Figure 1).
Conclusion: Our analysis acts as the first proposed replication of the previously described ~50% of West African PwP that carry at least one copy of a newly identified GBA1 intronic risk allele. Further analyses are underway to assess the genetic ancestry of the entirety of the PD GENEration cohort in an effort to better understand genetic risk factors of PD in underrepresented populations.
Race/Ethnicity for rs3115534-G cohort
References: Rizig, M. et al. Lancet Neurol 22, 1015-1025 (2023).
Alvarez Jerez, P. et al. Nat Struct Mol Biol 31, 1955-1963 (2024).
To cite this abstract in AMA style:
A. Dilliott, K. Ghosh Galvelis, N. Bothwick, R. Deleon, M. Dini, M. Thom, D. Anunciacion, E. Trinh, H. Gao, C. Blauwendraat, A. Singleton, J. Beck, R. Alcalay, P. Pdgeneration Study. Evaluating the GBA1 Intronic rs3115534-G PD Risk Variant in the PD GENEration Cohort [abstract]. Mov Disord. 2026; 41 (suppl 1). https://www.mdsabstracts.org/abstract/evaluating-the-gba1-intronic-rs3115534-g-pd-risk-variant-in-the-pd-generation-cohort/. Accessed October 1, 2026.« Back to 2026 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/evaluating-the-gba1-intronic-rs3115534-g-pd-risk-variant-in-the-pd-generation-cohort/