Article (Scientific journals)
Independent and joint effects of the MAPT and SNCA genes in Parkinson disease.
Elbaz, Alexis; Ross, Owen A.; Ioannidis, John P. A. et al.
2011In Annals of Neurology, 69 (5), p. 778-92
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Keywords :
Adult; Age of Onset; Aged; Aged, 80 and over; Case-Control Studies; Female; Genetic Predisposition to Disease; Humans; Logistic Models; Male; Middle Aged; Odds Ratio; Parkinson Disease/genetics; Polymorphism, Single Nucleotide/genetics; Retrospective Studies; alpha-Synuclein/genetics; tau Proteins/genetics
Abstract :
[en] 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.
Research center :
- Luxembourg Centre for Systems Biomedicine (LCSB): Clinical & Experimental Neuroscience (Krüger Group)
Disciplines :
Genetics & genetic processes
Author, co-author :
Elbaz, Alexis
Ross, Owen A.
Ioannidis, John P. A.
Soto-Ortolaza, Alexandra I.
Moisan, Frederic
Aasly, Jan
Annesi, Grazia
Bozi, Maria
Brighina, Laura
Chartier-Harlin, Marie-Christine
Destee, Alain
Ferrarese, Carlo
Ferraris, Alessandro
Gibson, J. Mark
Gispert, Suzana
Hadjigeorgiou, Georgios M.
Jasinska-Myga, Barbara
Klein, Christine
Krüger, Rejko ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Lambert, Jean-Charles
Lohmann, Katja
van de Loo, Simone
Loriot, Marie-Anne
Lynch, Timothy
Mellick, George D.
Mutez, Eugenie
Nilsson, Christer
Opala, Grzegorz
Puschmann, Andreas
Quattrone, Aldo
Sharma, Manu
Silburn, Peter A.
Stefanis, Leonidas
Uitti, Ryan J.
Valente, Enza Maria
Vilarino-Guell, Carles
Wirdefeldt, Karin
Wszolek, Zbigniew K.
Xiromerisiou, Georgia
Maraganore, Demetrius M.
Farrer, Matthew J.
More authors (31 more) Less
Language :
English
Title :
Independent and joint effects of the MAPT and SNCA genes in Parkinson disease.
Publication date :
2011
Journal title :
Annals of Neurology
ISSN :
1531-8249
Publisher :
John Wiley & Sons, Hoboken, United States - New York
Volume :
69
Issue :
5
Pages :
778-92
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Copyright (c) 2011 American Neurological Association.
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