African and multi-ancestry GWAS

The research record

This is the project's file for this landmark, as written and checked. Sources are listed at the end; anything not yet confirmed is marked "Not yet verified".

Who

Rizig, Bandres-Ciga, Makarious, Ojo and colleagues for the Global Parkinson's Genetics Program (GP2), the International Parkinson Disease Genomics Consortium Africa and 23andMe (Lancet Neurol 2023; funded by GP2, which is paid for by Aligning Science Across Parkinson's, and the Michael J. Fox Foundation); Kim, Vitale, Nalls, Foo, Mata and colleagues (Nat Genet 2024; funders include the Foundation, ASAP-GP2, the US NIH and Singapore's National Medical Research Council).

What happened

• African and admixed ancestry (2023). The analysis pooled 1,488 cases and 196,430 controls from GP2, an African research consortium and 23andMe. The main signal was a common GBA1-region variant, rs3115534-G (odds ratio 1.58), rare in other populations. The variant was present in 39% of cases. Whole-genome sequencing found no coding or structural change behind it. The signal was linked to lower glucocerebrosidase (GCase) activity.
• Multi-ancestry (2024). Kim et al. combined European, East Asian, Latin American and African data: 49,049 cases, 18,785 proxy cases (people with a parent with Parkinson's) and about 2.46 million controls. They found 78 independent loci, 12 of them new, fine-mapped likely causal variants at 6 known loci and linked 25 candidate genes to the new loci.

Why it moved us toward a cure

The 90-signal map of landmark 19 came almost entirely from people of European ancestry. These studies, enabled by the GP2 programme of landmark 78, test whether the targets generalise. The GBA1 result extends landmark 16: the lysosome pathway matters in African ancestry too, so GBA-directed drugs may apply more widely.

Outcome

Advanced (changed from open on 20 Oct 2026): the GBA1 signal has been followed up. A 2024 Nature Structural & Molecular Biology paper (Álvarez Jerez et al., DOI 10.1038/s41594-024-01423-2) showed that rs3115534 sits in the branchpoint of GBA1 intron 8, causes retained-intron transcripts, lowers GCase protein and activity in a dose-dependent way, and so may be a target for RNA-based treatment. A 2026 GP2 study of 99,783 people across 11 ancestries (Lange et al., Lancet Neurol, DOI 10.1016/S1474-4422(26)00198-5) extends the approach. These studies improve target choice and trial planning but are not a therapy. The 2023 GBA1 finding rests on a small African-ancestry case count (1,488 cases).

Sources

• Rizig et al., Lancet Neurol 2023;22:1015–1025, DOI 10.1016/S1474-4422(23)00283-1 (PMC10593199) · Michael J. Fox Foundation summary
• Kim et al., Nat Genet 2024;56:27–36, DOI 10.1038/s41588-023-01584-8 (abstract-level data via repository record)
• Álvarez Jerez et al., Nat Struct Mol Biol 2024, DOI 10.1038/s41594-024-01423-2 (abstract via Europe PMC)
• PMIDs 37633302 (Rizig) and 38155330 (Kim). No correction or retraction is listed for either.
• Not yet verified: the ancestry breakdown of the 2024 sample; whether the 12 new 2024 loci have replicated.