Abstract: Background: Common variants in the LRRK2 gene influence the risk of Parkinson's disease (PD) in Asians, but whether the same is true in European-derived populations is less clear. Methods: We genotyped 66 LRRK2 tagging single-nucleotide polymorphisms (SNPs) in 575 PD patients and 689 controls from the northwestern United States (tier 1). PD-associated SNPs (P < .05) were then genotyped in an independent sample of 3617 cases and 2512 controls from the United States and Spain (tier 2). Logistic regression was used to model additive SNP genotype effects adjusted for age and sex among white individuals. Results: Two regions showed independent association with PD in tier 1, and SNPs in both regions were successfully replicated in tier 2 (rs10878226, combined odds ratio [OR], 1.20; 95% confidence interval [CI], 1.08-1.33; P = 6.3 × 10-4; rs11176013, OR, 0.89; CI, 0.83-0.95; P = 4.6 × 10-4). Conclusions: Our data suggest that common variation within LRRK2 conveys susceptibility for PD in individuals of European ancestry.

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