rs1564282

This is a German dissertation containing two peer-reviewed association studies on Parkinson's disease genetics. The first study found EIF4G1 is neither a strong nor common PD risk factor in European cohorts (2146 patients), with the p.Arg1205His variant showing no significant association (OR=1.3, p=0.50) in Icelandic population. The second study demonstrated heterozygous PARK2 CNV carriers have increased PD risk in Iceland (1415 cases vs 40474 controls, OR=1.7, p=0.03), supported by meta-analysis.

German doctoral dissertation investigating genetic risk factors for Parkinson's disease in the Icelandic population. The thesis comprises three studies: (1) Analysis of EIF4G1 gene mutations (p.Ala502Val, p.Arg1205His) in 2,146 European PD patients and 93,698 Icelandic samples showing EIF4G1 is neither a strong nor common risk factor; (2) Case-control study of PARK2 copy number variants in 1,415 PD patients versus 40,474 controls (≥65 years) demonstrating heterozygous PARK2 CNV carriers have significantly increased PD risk (OR=1.69, p=0.03); (3) Investigation of common genetic PD risk variants' effects on LRRK2 G2019S mutation carriers.

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.

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.