rs356165

Meta-analysis of five Parkinson disease GWAS studies (4,238 cases, 4,239 controls) identifying a novel susceptibility locus at RIT2 (rs12456492, OR=1.19, p=2×10⁻¹⁰). Multiple independent associations detected at SNCA (rs356220, rs356198), GBA (E326K and N370S variants), and other loci including GAK/DGKQ, MAPT, and HLA region. Results replicated in 3,738 cases and 2,111 controls.

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.

Case-control association study of 302 SNPs in 137 candidate genes for sporadic Parkinson's disease in Japanese populations. The strongest association was rs1805874 in CALB1 (P = 7.1 × 10−5, OR = 1.34, recessive model) in combined analysis of 1,403 cases and 1,938 controls across two sample sets. SNCA rs7684318 showed prominent association (P = 5.1 × 10−14), and FGF20 was associated synergistically with SNCA.