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

Elbaz, Alexis; Ross, Owen A.; Ioannidis, John P. A.; Soto-Ortolaza, Alexandra I.; Moisan, Frederic; Aasly, Jan; Annesi, Grazia; Bozi, Maria; Brighina, Laura and Chartier-Harlin, Marie-Christine, et al. (2011) In Annals of Neurology 69(5). p.778-792
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... (More)
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 (Less)
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Annals of Neurology
volume
69
issue
5
pages
778 - 792
publisher
John Wiley and Sons Inc.
external identifiers
  • wos:000290156300005
  • scopus:79955389000
ISSN
1531-8249
DOI
10.1002/ana.22321
language
English
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yes
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8878d820-0fee-4bdf-808b-b2df4d597a7d (old id 1988126)
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2011-07-01 09:30:39
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@article{8878d820-0fee-4bdf-808b-b2df4d597a7d,
  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       = {Elbaz, Alexis and Ross, Owen A. and Ioannidis, John P. A. and Soto-Ortolaza, Alexandra I. and Moisan, Frederic and Aasly, Jan and Annesi, Grazia and Bozi, Maria and Brighina, Laura and Chartier-Harlin, Marie-Christine and Destee, Alain and Ferrarese, Carlo and Ferraris, Alessandro and Gibson, J. Mark and Gispert, Suzana and Hadjigeorgiou, Georgios M. and Jasinska-Myga, Barbara and Klein, Christine and Krueger, Rejko and Lambert, Jean-Charles and Lohmann, Katja and van de Loo, Simone and Loriot, Marie-Anne and Lynch, Timothy and Mellick, George D. and Mutez, Eugenie and Nilsson, Christer and Opala, Grzegorz and Puschmann, Andreas and Quattrone, Aldo and Sharma, Manu and Silburn, Peter A. and Stefanis, Leonidas and Uitti, Ryan J. and Valente, Enza Maria and Vilarino-Gueell, Carles and Wirdefeldt, Karin and Wszolek, Zbigniew K. and Xiromerisiou, Georgia and Maraganore, Demetrius M. and Farrer, Matthew J.},
  issn         = {1531-8249},
  language     = {eng},
  number       = {5},
  pages        = {778--792},
  publisher    = {John Wiley and Sons Inc.},
  series       = {Annals of Neurology},
  title        = {Independent and Joint Effects of the MAPT and SNCA Genes in Parkinson Disease},
  url          = {http://dx.doi.org/10.1002/ana.22321},
  volume       = {69},
  year         = {2011},
}