Validating an African Ancestry–Linked GBA1 Risk Variant in PD GENEration: Kamalini Galvelis, MS

A newly identified Parkinson disease (PD) risk variant in the 8th intron of GBA1, rs3115534-G, has been found in approximately 50% of West African patients living with PD. The variant causes intron 8 to be retained in the final transcript and reduces glucocerebrosidase (GCase) activity.^1,2 It first emerged from the first genome-wide association study of PD in African and African admixed populations. That study included 197,918 individuals and linked the variant to PD risk (odds ratio, 1.58) and earlier age at onset, yet found it rare in non-African populations.³

Replicating this finding is a role PD GENEration may be in positioned to fill. The international observational study offers genetic testing and counseling at no cost to people with PD across 10 countries and shares genomic data openly with researchers.⁴ At the 2026 International Congress of Parkinson's Disease and Movement Disorders, investigators reported on 26,637 of the 37,723 enrolled participants who were queried for the variant. Of these, 479 (1.8%) were heterozygous carriers and 69 (0.3%) were homozygous carriers.1

Carriers had an earlier mean age at onset than noncarriers (57.4 vs 60.3 years). Among the 21,917 participants with resolved genetic ancestry, carriers represented 51.1% of those of African ancestry and 35.1% of those of African admixed ancestry. Compared with gnomAD African/African American genomes, the variant was significantly associated with PD in participants of African genetic ancestry (OR, 3.22; 95% CI, 2.63-3.92). Adding the variant to the primary panel would raise the positive result rate among participants of African genetic ancestry from 9.9% to 56.7%, compared with 12.3% to 14.2% in the full cohort.

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"The fact that we found something so brand new in a diverse cohort means that there is so much more that we don't know, and we need to learn more."

To discuss these findings, NeurologyLive^® spoke with Kamalini Galvelis, MS, associate vice president of clinical research at the Parkinson's Foundation and lead author of the PD GENEration study. She described how the original discovery in a West African cohort raised new questions about the role of intronic variants in a gene that is itself still being characterized in PD. She also explained how PD GENEration aims to serve as a replication and validation resource for the broader research community.

From there, Galvelis walked through the results. Of roughly 26,000 participants evaluated, 548 carried the intronic variant, and more than half of carriers self-identified as Black or African American. She noted that genetically defined ancestry showed a similar pattern, which together represented the first independent validation of the original findings. She emphasized that the variant likely would not have been found had the original researchers not studied diverse populations. Galvelis closed by describing the team's next step: convening researchers, genetic counselors, and people living with PD in focus groups.

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REFERENCES
1. Dilliott AA, Ghosh Galvelis K, Azcarate I, et al. Evaluating the GBA1 intronic rs3115534-G PD risk variant in the PD GENEration cohort. Poster presented at: International Congress of Parkinson's Disease and Movement Disorders; October 4-8, 2026; Seoul, South Korea. Poster 1391.
2. Álvarez Jerez P, Wild Crea P, Ramos DM, et al. African ancestry neurodegeneration risk variant disrupts an intronic branchpoint in GBA1. Nat Struct Mol Biol. 2024;31(12):1955-1963. doi:10.1038/s41594-024-01423-2
3. Rizig M, Bandres-Ciga S, Makarious MB, et al. Identification of genetic risk loci and causal insights associated with Parkinson's disease in African and African admixed populations: a genome-wide association study. Lancet Neurol. 2023;22(11):1015-1025. doi:10.1016/S1474-4422(23)00283-1
4. Galvelis KG, Dilliott AA, Dini M, et al. PD GENEration: an international Parkinson's disease genetic research study. medRxiv. Preprint posted online 2026. doi:10.64898/2026.05.20.26353696