Common variation in the LRRK2 gene is a risk factor for Parkinson's disease

Mov Disord. 2012 Oct 31. doi: 10.1002/mds.25226. [Epub ahead of print]

Mata IF, Checkoway H, Hutter CM, Samii A, Roberts JW, Kim HM, Agarwal P, Alvarez V, Ribacoba R, Pastor P, Lorenzo-Betancor O, Infante J, Sierra M, Gómez-Garre P, Mir P, Ritz B, Rhodes SL, Colcher A, Van Deerlin V, Chung KA, Quinn JF, Yearout D, Martinez E, Farin FM, Wan JY, Edwards KL, Zabetian CP.

Source

Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA; Department of Neurology, University of Washington School of Medicine, Seattle, Washington, USA.

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. © 2012 Movement Disorder Society.

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