title: Replication of MAPT and SNCA, but not PARK16-18, as susceptibility genes for Parkinson's disease.
abstract: Recent genome-wide association studies of Parkinson's disease have nominated 3 new susceptibility loci (PARK16-18) and confirmed 2 known risk genes (MAPT and SNCA) in populations of European ancestry. We sought to replicate these findings. We genotyped single-nucleotide polymorphisms in each of these genes/loci in 1445 Parkinson's disease patients and 1161 controls from northern Spain. Logistic regression was used to test for association between genotype and Parkinson's disease under an additive model, adjusting for sex, age, and site. We also performed analyses stratified by age at onset. Single-nucleotide polymorphisms in MAPT (rs1800547; P = 3.1 × 10(-4) ) and SNCA (rs356219; P = 5.5 × 10(-4) ) were significantly associated with Parkinson's disease. However, none of the markers in PARK16-18 associated with Parkinson's disease in the overall sample, or in any age stratum, with P values ranging from .09 to .88. Although our data further validate MAPT and SNCA as Parkinson's disease susceptibility genes, we failed to replicate PARK16, PARK17, and PARK18. Potential reasons for the discordance between our study and previous genome-wide association studies include effects of population structure, power, and population-specific environmental interactions. Our findings suggest that additional studies of PARK16-18 are necessary to establish the role of these loci in modifying risk for Parkinson's disease in European-derived populations. © 2011 Movement Disorder Society.
authors.affiliation: Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA.
authors.forename: Ignacio F
authors.initials: IF
authors.lastname: Mata
authors.forename: Dora
authors.initials: D
authors.lastname: Yearout
authors.forename: Victoria
authors.initials: V
authors.lastname: Alvarez
authors.forename: Eliecer
authors.initials: E
authors.lastname: Coto
authors.forename: Lorena
authors.initials: L
authors.lastname: de Mena
authors.forename: Renee
authors.initials: R
authors.lastname: Ribacoba
authors.forename: Oswaldo
authors.initials: O
authors.lastname: Lorenzo-Betancor
authors.forename: Lluis
authors.initials: L
authors.lastname: Samaranch
authors.forename: Pau
authors.initials: P
authors.lastname: Pastor
authors.forename: Sebastian
authors.initials: S
authors.lastname: Cervantes
authors.forename: Jon
authors.initials: J
authors.lastname: Infante
authors.forename: Ines
authors.initials: I
authors.lastname: Garcia-Gorostiaga
authors.forename: Maria
authors.initials: M
authors.lastname: Sierra
authors.forename: Onofre
authors.initials: O
authors.lastname: Combarros
authors.forename: Katherine W
authors.initials: KW
authors.lastname: Snapinn
authors.forename: Karen L
authors.initials: KL
authors.lastname: Edwards
authors.forename: Cyrus P
authors.initials: CP
authors.lastname: Zabetian
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D004261:DNA Replication / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010300:Parkinson Disease / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D013030:Spain; D051844:alpha-Synuclein / Q000235:genetics*; D016875:tau Proteins / Q000235:genetics*
chemical_list: C054369:MAPT protein, human; C497604:SNCA protein, human; D051844:alpha-Synuclein; D016875:tau Proteins