*contributed equally

To determine whether the RAB32 p.Ser71Arg variant contributes to Parkinson’s disease (PD) susceptibility in underrepresented populations from Africa,Europe, and South America.

PD is a genetically complex disorder, with 19–37% of heritability explained by known DNA variation. Rare variants, such as RAB32 p.Ser71Arg, have been suggested as novel risk factors, especially in Mediterranean and North American cohorts. RAB32 encodes a Rab GTPase regulating mitochondrial dynamics, and vesicular trafficking, and functionally interacts with LRRK2. Reported carriers typically presented with late-onset parkinsonism, family history, and good levodopa response, although autopsy findings lacked classical Lewy body pathology (similarly to half of LRRK2 carriers).The contribution of RAB32 to PD remains uncertain, and no data exist from many world regions.

We analyzed 1,730 PD patients from seven cohorts:Colombia (n=188), Czech Republic (n=31), Ecuador (n=390), Nigeria (n=52), Ireland (n=314), Poland (n=627), and Ukraine (n=128). Controls (n=523) were available from Colombia (62), Ireland (231), Poland (200), and Ukraine (30). Genotyping for RAB32 p.Ser71Arg was performed with ABI TaqMan SNP assays with positive controls. Individuals carrying pathogenic variants in other PD genes were excluded. All participants provided informed consent, and IRB approval was obtained. Genotyping was performed in the USA.

No RAB32 p.Ser71Arg carriers were identified among 1,730 patients and 523 controls.Median age-at-onset was broadly similar (late 50s–early 60s),except for Colombia, where median onset was 50 years and 45% were early-onset cases, reflecting targeted recruitment. Familial aggregation varied: Ireland (57%) and Ukraine (45%) were highest, Colombia intermediate (40%), Poland low (9%), and Nigeria none possibly reflecting underdiagnosis/underreporting or recruitment bias.

This first large-scale evaluation of RAB32 in Africa, Eastern Europe, and South America found no carriers, suggesting minimal contribution of RAB32 p.Ser71Arg in these regions. These findings highlight global variability in PD presentation and the need for large, multiethnic studies to fully assess rare genetic risk factors.