Independent and joint effects of the MAPT and SNCA genes in Parkinson disease (Journal article)

Elbaz, A./ Ross, O. A./ Ioannidis, J. P./ Soto-Ortolaza, A. I./ Moisan, F./ Aasly, J. O./ Annesi, G./ Bozi, M./ Brighina, L./ Chartier-Harlin, M. C./ Destee, A./ Ferrarese, C./ Ferraris, A./ Gibson, J. M./ Gispert, S./ Hadjigeorgiou, G. M./ Jasinska-Myga, B./ Klein, C./ Kruger, R./ Lambert, J. C./ Lohmann, K./ van de Loo, S./ Loriot, M. A./ Lynch, T./ Mellick, G. D./ Mutez, E./ Nilsson, C./ Opala, G./ Puschmann, A./ Quattrone, A./ Sharma, M./ Silburn, P. A./ Stefanis, L./ Uitti, R. J./ Valente, E. M./ Vilarino-Guell, C./ Wirdefeldt, K./ Wszolek, Z. K./ Xiromerisiou, G./ Maraganore, D. M./ Farrer, M. J.

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.
Institution and School/Department of submitter: Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής
Keywords: Adult,Age of Onset,Aged,Aged, 80 and over,Case-Control Studies,Female,*Genetic Predisposition to Disease,Humans,Logistic Models,Male,Middle Aged,Odds Ratio,Parkinson Disease/*genetics,Polymorphism, Single Nucleotide/*genetics,Retrospective Studies,alpha-Synuclein/*genetics,tau Proteins/*genetics
ISSN: 1531-8249
Appears in Collections:Άρθρα σε επιστημονικά περιοδικά ( Ανοικτά)

Files in This Item:
File Description SizeFormat 
Elbaz-2011-Independent and join.pdf639.15 kBAdobe PDFView/Open    Request a copy

 Please use this identifier to cite or link to this item:
  This item is a favorite for 0 people.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.