Independent and Joint Effects of the MAPT and SNCA Genes in Parkinson Disease

Research output: Contribution to journalArticle


title = "Independent and Joint Effects of the MAPT and SNCA Genes in Parkinson Disease",
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 30 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. ANN NEUROL 2011; 69: 778-792",
author = "Alexis Elbaz and Ross, {Owen A.} and Ioannidis, {John P. A.} and Soto-Ortolaza, {Alexandra I.} and Frederic Moisan and Jan Aasly and Grazia Annesi and Maria Bozi and Laura Brighina and Marie-Christine Chartier-Harlin and Alain Destee and Carlo Ferrarese and Alessandro Ferraris and Gibson, {J. Mark} and Suzana Gispert and Hadjigeorgiou, {Georgios M.} and Barbara Jasinska-Myga and Christine Klein and Rejko Krueger and Jean-Charles Lambert and Katja Lohmann and {van de Loo}, Simone and Marie-Anne Loriot and Timothy Lynch and Mellick, {George D.} and Eugenie Mutez and Christer Nilsson and Grzegorz Opala and Andreas Puschmann and Aldo Quattrone and Manu Sharma and Silburn, {Peter A.} and Leonidas Stefanis and Uitti, {Ryan J.} and Valente, {Enza Maria} and Carles Vilarino-Gueell and Karin Wirdefeldt and Wszolek, {Zbigniew K.} and Georgia Xiromerisiou and Maraganore, {Demetrius M.} and Farrer, {Matthew J.}",
note = "The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Department of Psychogeriatrics (013304000), Neurology, Lund (013027000)",
year = "2011",
doi = "10.1002/ana.22321",
language = "English",
volume = "69",
pages = "778--792",
journal = "Annals of Neurology",
issn = "1531-8249",
publisher = "John Wiley and Sons Inc.",
number = "5",