rs2736990

This replication study of 1,445 Parkinson's disease patients and 1,161 controls from Northern Spain confirms MAPT (rs1800547, p=3.1×10⁻⁴, OR=0.79) and SNCA (rs356219, p=5.5×10⁻⁴, OR=1.23) as PD susceptibility genes, but fails to replicate PARK16, PARK17, and PARK18 loci (p values 0.09-0.88). The findings suggest that PARK16-18 may harbor population-specific effects or require larger sample sizes for detection in European-derived populations.

This study replicates the association between the SNCA rs2736990 variant and Parkinson's disease in the Harvard NeuroDiscovery Center Biomarker Study (344 PD cases, 275 controls). The minor G allele was significantly associated with increased PD risk (OR = 1.40, 95% CI: 1.12-1.76, P = 0.0032), with a 40% increase in risk per allele. The intronic variant supports a genetic role for non-coding SNCA variants in common sporadic Parkinson's disease.

This case-control association study of 1,956 Parkinson's disease (PD) patients and 2,112 controls identified rs356219 (OR=1.41, 95% CI 1.28-1.55, p=1.6×10⁻¹²) as a major genetic susceptibility variant for PD located ~9 kb downstream of SNCA. The risk allele was associated with increased plasma α-synuclein levels in PD cases (p=0.005), suggesting the functional variant tagged by rs356219 may upregulate SNCA expression in a dose-dependent manner, independent of the previously known REP1 promoter repeat polymorphism.