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

Alexis Elbaz*, Owen A. Ross, John P.A. Ioannidis, Alexandra I. Soto-Ortolaza, Frédéric Moisan, Jan Aasly, Grazia Annesi, Maria Bozi, Laura Brighina, Marie Christine Chartier-Harlin, Alain Destée, Carlo Ferrarese, Alessandro Ferraris, J. Mark Gibson, Suzana Gispert, Georgios M. Hadjigeorgiou, Barbara Jasinska-Myga, Christine Klein, Rejko Krüger, Jean Charles LambertKatja Lohmann, Simone Van De Loo, Marie Anne Loriot, Timothy Lynch, George D. Mellick, Eugénie Mutez, Christer Nilsson, Grzegorz Opala, Andreas Puschmann, Aldo Quattrone, Manu Sharma, Peter A. Silburn, Leonidas Stefanis, Ryan J. Uitti, Enza Maria Valente, Carles Vilariño-Güell, Karin Wirdefeldt, Zbigniew K. Wszolek, Georgia Xiromerisiou, Demetrius M. Maraganore, Matthew J. Farrer

*Corresponding author for this work
59 Citations (Scopus)


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.

Original languageEnglish
JournalAnnals of Neurology
Issue number5
Pages (from-to)778-792
Number of pages15
Publication statusPublished - 01.05.2011


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