Movement Disorders (revue)

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Replication of MAPT and SNCA, but not PARK16-18, as Susceptibility Genes for Parkinson’s Disease

Identifieur interne : 000129 ( Pmc/Corpus ); précédent : 000128; suivant : 000130

Replication of MAPT and SNCA, but not PARK16-18, as Susceptibility Genes for Parkinson’s Disease

Auteurs : Ignacio F. Mata ; Dora Yearout ; Victoria Alvarez ; Eliecer Coto ; Lorena De Mena ; Renee Ribacoba ; Oswaldo Lorenzo-Betancor ; Lluis Samaranch ; Pau Pastor ; Sebastian Cervantes ; Jon Infante ; Ines Garcia-Gorostiaga ; Maria Sierra ; Onofre Combarros ; Katherine W. Snapinn ; Karen L. Edwards ; Cyrus P. Zabetian

Source :

RBID : PMC:3082603

Abstract

Background

Recent genome-wide association studies of Parkinson’s disease have nominated three new susceptibility loci (PARK16-18) and confirmed two known risk genes (MAPT and SNCA) in populations of European ancestry. We sought to replicate these findings.

Methods

We genotyped single nucleotide polymorphisms in each of these genes/loci in 1,445 Parkinson’s disease patients and 1,161 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.

Results

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 0.09–0.88.

Conclusions

While our data further validate MAPT and SNCA as Parkinson’s disease susceptibility genes, we failed to replicate PARK16, 17, and 18. 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.


Url:
DOI: 10.1002/mds.23642
PubMed: 21425343
PubMed Central: 3082603

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