title: Common variation in the LRRK2 gene is a risk factor for Parkinson's disease.
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.
authors.affiliation: Veterans Affairs Puget Sound Health Care System, Seattle, Washington 98108, USA. nachofm@u.washington.edu
authors.forename: Ignacio F
authors.initials: IF
authors.lastname: Mata
authors.forename: Harvey
authors.initials: H
authors.lastname: Checkoway
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Hutter
authors.forename: Ali
authors.initials: A
authors.lastname: Samii
authors.forename: John W
authors.initials: JW
authors.lastname: Roberts
authors.forename: Hojoong M
authors.initials: HM
authors.lastname: Kim
authors.forename: Pinky
authors.initials: P
authors.lastname: Agarwal
authors.forename: Victoria
authors.initials: V
authors.lastname: Alvarez
authors.forename: Renee
authors.initials: R
authors.lastname: Ribacoba
authors.forename: Pau
authors.initials: P
authors.lastname: Pastor
authors.forename: Oswaldo
authors.initials: O
authors.lastname: Lorenzo-Betancor
authors.forename: Jon
authors.initials: J
authors.lastname: Infante
authors.forename: María
authors.initials: M
authors.lastname: Sierra
authors.forename: Pilar
authors.initials: P
authors.lastname: Gómez-Garre
authors.forename: Pablo
authors.initials: P
authors.lastname: Mir
authors.forename: Beate
authors.initials: B
authors.lastname: Ritz
authors.forename: Shannon L
authors.initials: SL
authors.lastname: Rhodes
authors.forename: Amy
authors.initials: A
authors.lastname: Colcher
authors.forename: Vivianna
authors.initials: V
authors.lastname: Van Deerlin
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Chung
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Quinn
authors.forename: Dora
authors.initials: D
authors.lastname: Yearout
authors.forename: Erica
authors.initials: E
authors.lastname: Martinez
authors.forename: Federico M
authors.initials: FM
authors.lastname: Farin
authors.forename: Jia Y
authors.initials: JY
authors.lastname: Wan
authors.forename: Karen L
authors.initials: KL
authors.lastname: Edwards
authors.forename: Cyrus P
authors.initials: CP
authors.lastname: Zabetian
mesh_terms: D000368:Aged; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing / Q000379:methods; D005838:Genotype; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012307:Risk Factors; D013030:Spain; D014481:United States
chemical_list: C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases