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.
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.
Authors: Benoit I Giasson; Mark S Forman; Makoto Higuchi; Lawrence I Golbe; Charles L Graves; Paul T Kotzbauer; John Q Trojanowski; Virginia M-Y Lee Journal: Science Date: 2003-04-25 Impact factor: 47.728
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Authors: D G Healy; P M Abou-Sleiman; A J Lees; J P Casas; N Quinn; K Bhatia; A D Hingorani; N W Wood Journal: J Neurol Neurosurg Psychiatry Date: 2004-07 Impact factor: 10.154
Authors: Lisa Wang; Michael G Heckman; Jan O Aasly; Grazia Annesi; Maria Bozi; Sun Ju Chung; Carl Clarke; David Crosiers; Gertrud Eckstein; Gaetan Garraux; Georgios M Hadjigeorgiou; Nobu Hattori; Beom Jeon; Yun J Kim; Masato Kubo; Suzanne Lesage; Juei Jueng Lin; Timothy Lynch; Peter Lichtner; George D Mellick; Vincent Mok; Karin E Morrison; Aldo Quattrone; Wataru Satake; Peter A Silburn; Leonidas Stefanis; Joanne D Stockton; Eng King Tan; Tatsushi Toda; Alexis Brice; Christine Van Broeckhoven; Ryan J Uitti; Karin Wirdefeldt; Zbigniew Wszolek; Georgia Xiromerisiou; Demetrius M Maraganore; Thomas Gasser; Rejko Krüger; Matthew J Farrer; Owen A Ross; Manu Sharma Journal: Neurobiol Aging Date: 2016-10-06 Impact factor: 4.673
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Authors: Angela Roco; Félix Javier Jiménez-Jiménez; Hortensia Alonso-Navarro; Carmen Martínez; Martín Zurdo; Laura Turpín-Fenoll; Jorge Millán; Teresa Adeva-Bartolomé; Esther Cubo; Francisco Navacerrada; Ana Rojo-Sebastián; Lluisa Rubio; Marisol Calleja; José Francisco Plaza-Nieto; Belén Pilo-de-la-Fuente; Margarita Arroyo-Solera; Elena García-Martín; José A G Agúndez Journal: J Neural Transm (Vienna) Date: 2012-09-22 Impact factor: 3.575
Authors: Michael G Heckman; Alexis Elbaz; Alexandra I Soto-Ortolaza; Daniel J Serie; Jan O Aasly; Grazia Annesi; Georg Auburger; Justin A Bacon; Magdalena Boczarska-Jedynak; Maria Bozi; Laura Brighina; Marie-Christine Chartier-Harlin; Efthimios Dardiotis; Alain Destée; Carlo Ferrarese; Alessandro Ferraris; Brian Fiske; Suzana Gispert; Georgios M Hadjigeorgiou; Nobutaka Hattori; John P A Ioannidis; Barbara Jasinska-Myga; Beom S Jeon; Yun Joong Kim; Christine Klein; Rejko Kruger; Elli Kyratzi; Chin-Hsien Lin; Katja Lohmann; Marie-Anne Loriot; Timothy Lynch; George D Mellick; Eugénie Mutez; Grzegorz Opala; Sung Sup Park; Simona Petrucci; Aldo Quattrone; Manu Sharma; Peter A Silburn; Young Ho Sohn; Leonidas Stefanis; Vera Tadic; Hiroyuki Tomiyama; Ryan J Uitti; Enza Maria Valente; Demetrios K Vassilatis; Carles Vilariño-Güell; Linda R White; Karin Wirdefeldt; Zbigniew K Wszolek; Ruey-Meei Wu; Georgia Xiromerisiou; Demetrius M Maraganore; Matthew J Farrer; Owen A Ross Journal: Neurobiol Aging Date: 2013-08-17 Impact factor: 4.673