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

Research output: Contribution to journalArticle


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


  • Alexis Elbaz
  • Owen A. Ross
  • John P. A. Ioannidis
  • Alexandra I. Soto-Ortolaza
  • Frederic Moisan
  • Jan Aasly
  • Grazia Annesi
  • Maria Bozi
  • Laura Brighina
  • Marie-Christine Chartier-Harlin
  • Alain Destee
  • Carlo Ferrarese
  • Alessandro Ferraris
  • J. Mark Gibson
  • Suzana Gispert
  • Georgios M. Hadjigeorgiou
  • Barbara Jasinska-Myga
  • Christine Klein
  • Rejko Krueger
  • Jean-Charles Lambert
  • Katja Lohmann
  • Simone van de Loo
  • Marie-Anne Loriot
  • Timothy Lynch
  • George D. Mellick
  • Eugenie Mutez
  • Christer Nilsson
  • Grzegorz Opala
  • Aldo Quattrone
  • Manu Sharma
  • Peter A. Silburn
  • Leonidas Stefanis
  • Ryan J. Uitti
  • Enza Maria Valente
  • Carles Vilarino-Gueell
  • Karin Wirdefeldt
  • Zbigniew K. Wszolek
  • Georgia Xiromerisiou
  • Demetrius M. Maraganore
  • Matthew J. Farrer
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Geriatrics
  • Psychiatry
  • Neurology
Original languageEnglish
Pages (from-to)778-792
JournalAnnals of Neurology
Issue number5
Publication statusPublished - 2011
Publication categoryResearch

Bibliographic 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)

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