rs11248051

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 study in 1,574 Han Chinese subjects (812 PD patients, 762 controls) demonstrates that the rs1564282 variant in GAK is associated with increased Parkinson's disease risk (OR=1.34-1.59 depending on model, P=0.007-0.017). A meta-analysis combining this result with published data confirmed the association across populations (OR=1.31, 95% CI=1.19-1.44, P<0.00001), though clinical features and motor severity were similar between carriers and non-carriers.

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.

First genome-wide association study (GWAS) of familial Parkinson disease in 857 cases and 867 controls identified association with SNPs in GAK/DGKQ (p=3.4×10⁻⁶, OR=1.69), SNCA (p=5.5×10⁻⁵, OR=1.35), and MAPT (p=2.0×10⁻⁵, OR=0.56). Meta-analysis with Fung et al. strengthened evidence for GAK/DGKQ (p=2.5×10⁻⁷) and MAPT regions, confirming previously implicated genes and nominating new susceptibility loci for PD.