Objective: To evaluate the frequency of leucine-rich repeat kinase gene (LRRK2) mutations and single nucleotide polymorphisms (SNPs) in early-onset Parkinson disease (EOPD) and late-onset Parkinson disease (LOPD).
Methods: We genotyped five previously reported LRRK2 mutations (G2019S, L1114L, I1122V, R1441C, and Y1699C) and 17 coding SNPs for haplotype analysis in 504 cases with PD and 314 controls enrolled in the Genetic Epidemiology of PD Study. Cases and controls were recruited without knowledge of family history of PD and cases were oversampled in the < or =50 age at onset (AAO) category.
Results: The LRRK2 G2019S mutation was present in 28 cases with PD (5.6%) and two controls (0.6%) (chi(2) = 13.25; p < 0.01; odds ratio 9.18, 95% CI: 2.17 to 38.8). The mutations L1114L, I1122V, R1441C, and Y1699C were not identified. The frequency of the LRRK2 G2019S mutation was 4.9% in 245 cases with AAO < or =50 years vs 6.2% in 259 cases with AAO >50 (p = 0.56). All cases with PD with the G2019S mutation shared the same disease-associated haplotype. The frequency of the LRRK2 G2019S mutation was higher in the subset of 181 cases reporting four Jewish grandparents (9.9%) than in other cases (3.1%) (p < 0.01). Age-specific penetrance to age 80 was 24% and was similar in Jewish and non-Jewish cases.
Conclusions: The G2019S mutation is a risk factor in both early- and late-onset Parkinson disease and confirms the previous report of a greater frequency of the G2019S mutation in Jewish than in non-Jewish cases with Parkinson disease.