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Independent and joint effects of the MAPT and SNCA genes in Parkinson disease

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Author
Elbaz, A.; Ross, O. A.; Ioannidis, J. P. A.; Soto-Ortolaza, A. I.; Moisan, F.; Aasly, J.; Annesi, G.; Bozi, M.; Brighina, L.; Chartier-Harlin, M. C.; Destée, A.; Ferrarese, C.; Ferraris, A.; Gibson, J. M.; Gispert, S.; Hadjigeorgiou, G. M.; Jasinska-Myga, B.; Klein, C.; Krüger, R.; Lambert, J. C.; Lohmann, K.; Van De Loo, S.; Loriot, M. A.; Lynch, T.; Mellick, G. D.; Mutez, E.; Nilsson, C.; Opala, G.; Puschmann, A.; Quattrone, A.; Sharma, M.; Silburn, P. A.; Stefanis, L.; Uitti, R. J.; Valente, E. M.; Vilariño-Güell, C.; Wirdefeldt, K.; Wszolek, Z. K.; Xiromerisiou, G.; Maraganore, D. M.; Farrer, M. J.
Date
2011
DOI
10.1002/ana.22321
Keyword
alpha synuclein
tau protein
adult
article
Caucasian
controlled study
disease predisposition
gene interaction
genotype
haplotype
human
Parkinson disease
priority journal
single nucleotide polymorphism
Age of Onset
Aged
Aged, 80 and over
alpha-Synuclein
Case-Control Studies
Female
Genetic Predisposition to Disease
Humans
Logistic Models
Male
Middle Aged
Odds Ratio
Polymorphism, Single Nucleotide
Retrospective Studies
tau Proteins
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Abstract
Objective: We studied the independent and joint effects of the genes encoding alpha-synuclein (SNCA) and microtubule-associated protein tau (MAPT) in Parkinson disease (PD) as part of a large meta-analysis of individual data from case-control studies participating in the Genetic Epidemiology of Parkinson's Disease (GEO-PD) consortium. Methods: Participants of Caucasian ancestry were genotyped for a total of 4 SNCA (rs2583988, rs181489, rs356219, rs11931074) and 2 MAPT (rs1052553, rs242557) single nucleotide polymorphism (SNPs). Individual and joint effects of SNCA and MAPT SNPs were investigated using fixed- and random-effects logistic regression models. Interactions were studied on both a multiplicative and an additive scale, and using a case-control and case-only approach. Results: Fifteen GEO-PD sites contributed a total of 5,302 cases and 4,161 controls. All 4 SNCA SNPs and the MAPT H1-haplotype-defining SNP (rs1052553) displayed a highly significant marginal association with PD at the significance level adjusted for multiple comparisons. For SNCA, the strongest associations were observed for SNPs located at the 3′ end of the gene. There was no evidence of statistical interaction between any of the 4 SNCA SNPs and rs1052553 or rs242557, neither on the multiplicative nor on the additive scale. Interpretation: This study confirms the association between PD and both SNCA SNPs and the H1 MAPT haplotype. It shows, based on a variety of approaches, that the joint action of variants in these 2 loci is consistent with independent effects of the genes without additional interacting effects. © 2011 American Neurological Association.
URI
http://hdl.handle.net/11615/27297
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