rs11868035

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.

Large European association study evaluating EIF4G1 mutations in Parkinson's disease across 2,146 PD patients and 93,698 Icelandic population samples. The p.Arg1205His variant (rs112176450) showed no significant association with PD risk (OR=1.3, p=0.50), and p.Ala502Val was not detected. The study concludes EIF4G1 is neither a strong nor common PD risk factor and should not be recommended for clinical diagnostic testing.

This candidate gene association study examined SREBF1c polymorphisms in relation to type 2 diabetes risk. Six SNPs spanning the SREBF1c gene were genotyped in two case-control studies (n=1,938 combined) and a cohort study (n=1,721). The intronic SNP rs11868035 showed significantly increased diabetes risk (OR=1.20, p=0.015), as did three SNPs in the 5' region (rs2236513, rs6502618, rs1889018, all OR≥1.21, p≤0.006). These SNPs were also weakly associated with plasma glucose concentrations in the cohort study.