Multi-locus genetic dosage shapes cognitive disease progression in Parkinson's patients: 15-year meta-analysis of 24 cohorts - PubMed
3 days ago
- #Parkinson's disease
- #genetic dosage
- #cognitive decline
- A 15-year meta-analysis involving 7745 Parkinson's disease patients from 24 cohorts revealed that multi-locus genetic dosage influences cognitive decline progression.
- Five specific genetic loci (RIMS2, TMEM108, GBA1, APOE, WWOX) linked to synaptic vulnerability and amyloid-tau pathology were analyzed for their cumulative effects.
- Dementia risk increases monotonically with the number of progression loci: single locus HR=1.56, two loci HR=3.21, and three or more loci HR=7.49.
- Individual loci show varying hazard ratios for dementia risk: GBA1 (HR=2.09), APOE ε4 (HR=1.71), RIMS2 (HR=1.90), TMEM108 (HR=2.05), WWOX (HR=1.56).
- The study suggests that multi-locus dosage could enhance patient stratification and clinical trial design in Parkinson's disease.