1. Independent and joint effects of the MAPT and SNCA genes in Parkinson disease
- Author
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Elbaz, Alexis, Ross, Owen A, Destée, Alain, Ferrarese, Carlo, Ferraris, Alessandro, Gibson, J Mark, Gispert, Suzana, Hadjigeorgiou, Georgios M, Jasinska-Myga, Barbara, Klein, Christine, Krüger, Rejko, Lambert, Jean-Charles, Ioannidis, John P A, Lohmann, Katja, van de Loo, Simone, Loriot, Marie-Anne, Lynch, Timothy, Mellick, George D, Mutez, Eugénie, Nilsson, Christer, Opala, Grzegorz, Puschmann, Andreas, Quattrone, Aldo, Soto-Ortolaza, Alexandra I, Sharma, Manu, Silburn, Peter A, Stefanis, Leonidas, Uitti, Ryan J, Valente, Enza Maria, Vilariño-Güell, Carles, Wirdefeldt, Karin, Wszolek, Zbigniew K, Xiromerisiou, Georgia, Maraganore, Demetrius M, Moisan, Frédéric, Farrer, Matthew J, Disease, Genetic Epidemiology of Parkinson's, Amouyel, Philippe, Tzourio, Christophe, Mulot, Claire, Bacon, Justin A, Cobb, Stephanie A, Sutherland, Greg T, Siebert, Gerhard A, Dissanayaka, Nadeeka, Aasly, Jan, O'Sullivan, John D, Boyle, Richard S, Pasquier, Florence, Bordet, Régis, Legendre, Jean-Philippe, Auburger, Georg, Hilker, Rüdiger, Abahuni, Nadine, Geisen, Christof, Winkler, Susen, Annesi, Grazia, Gasser, Thomas, Riess, Olaf, Berg, Daniela, Schulte, Claudia, Vassilatis, Demitris, Stamboulis, Eleftherios, Dardiotis, Efthimios, Patramani, Ioanna, Kountra, Persa-Maria, Vogiatzi, Christina, Bozi, Maria, Markou, Katerina, Tarantino, Patrizia, Annesi, Ferdinanda, Bentivoglio, Anna Rita, Guidubaldi, Arianna, Caccialupi, Matilde, De Nigris, Francesca, Riva, Chiara, Pedersen, Nancy L, Nilsson, Karin, Brighina, Laura, Reimer, Jan, Van Gerpen, Jay, Lash, Jennifer, Searcy, Jill, Strongosky, Audrey, Chartier-Harlin, Marie-Christine, Elbaz, A, Ross, O, Ioannidis, J, Soto Ortolaza, A, Moisan, F, Aasly, J, Annesi, G, Bozi, M, Brighina, L, Chartier Harlin, M, Destée, A, Ferrarese, C, Ferraris, A, Gibson, J, Gispert, S, Hadjigeorgiou, G, Jasinska Myga, B, Klein, C, Krüger, R, Lambert, J, Lohmann, K, van de Loo, S, Loriot, M, Lynch, T, Mellick, G, Mutez, E, Nilsson, C, Opala, G, Puschmann, A, Quattrone, A, Sharma, M, Silburn, P, Stefanis, L, Uitti, R, Valente, E, Vilariño Güell, C, Wirdefeldt, K, Wszolek, Z, Xiromerisiou, G, Maraganore, D, and Farrer, M
- Subjects
Adult ,Male ,Parkinson Disease/*genetics ,Logistic Model ,Polymorphism, Single Nucleotide/*genetics ,Single-nucleotide polymorphism ,Genome-wide association study ,MAPT protein, human ,tau Proteins ,Biology ,alpha-Synuclein/*genetics ,Polymorphism, Single Nucleotide ,Article ,Gene interaction ,genetics [Parkinson Disease] ,Retrospective Studie ,Genotype ,Odds Ratio ,SNP ,Humans ,genetics ,Genetic Predisposition to Disease ,ddc:610 ,SNCA protein, human ,Age of Onset ,Retrospective Studies ,Aged ,Genetics ,Aged, 80 and over ,Haplotype ,tau Protein ,Parkinson Disease ,Middle Aged ,genetics [tau Proteins] ,Settore MED/26 - NEUROLOGIA ,Logistic Models ,Neurology ,Genetic epidemiology ,Case-Control Studies ,Multiple comparisons problem ,genetics [Polymorphism, Single Nucleotide] ,genetics [alpha-Synuclein] ,alpha-Synuclein ,Female ,Neurology (clinical) ,tau Proteins/*genetics ,Case-Control Studie ,Human - 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
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- 2011