Journal
ANNALS OF NEUROLOGY
Volume 69, Issue 5, Pages 778-792Publisher
WILEY-BLACKWELL
DOI: 10.1002/ana.22321
Keywords
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Funding
- GEO-PD (Genetic Epidemiology of Parkinson's Disease)
- National Research Agency (ANR)
- French Agency for Environmental and Occupational Health Safety (Afsset)
- France Parkinson USA
- Stephanie A. Cobb (Mayo Clinic, Jacksonville)
- Michael J. Fox Foundation
- American Parkinson's Disease Association
- Morris K. Udall Parkinson's Disease Research Center of Excellence (National Institute of Neurological Disorders and Stroke [NINDS] [NS40256]
- National Institutes of Health (NIH) [2R01ES10751, ES10758]
- NIH/National Center for Research Resources [UL1 RR025752]
- National Health and Medical Research Council (Australia) [401537]
- Geriatric Medical Foundation of Queensland
- Princess Alexandra Hospital
- Royal Brisbane Foundation
- Women's Hospital Foundation
- Foundation for Medical Research (FRM) [2006/413]
- PHRC [005/1913, 2002/1918]
- University of Lille 2
- INSERM-French Research Ministry
- BMBF NGFNplus [01GS08138]
- Volkswagen Foundation
- Hermann and Lilly Schilling Foundation
- German Research Council [DFG] [KR2119/3-2]
- Federal Ministry for Education and Research (BMBF, NGFNplus) [01GS08134]
- Hellenic Secretariat of Research and Technology
- University of Thessaly, Research Committee [2845]
- Institute of Biomedical Research and Technology, CERETETH [01-04-207]
- Italian Ministry of Health
- FIRB [RBLA038RMA_003]
- Research Council of Norway [10314000]
- Swedish Research Council
- Swedish Society for Medical Research
- Swedish Society of Medicine
- Karolinska Institutet
- Parkinson Foundation in Sweden
- Swedish Parkinson Academy
- AFA Insurance Research Grant
- Elsa Schmitz Foundation
- Apotekare Hedberg's Foundation for Medical Research
- Swedish Parkinson Fund (
- Royal Physiographic Society in Lund
- Lund University Hospital Research
- Mayo Clinic Jacksonville
- Morris K. Udall Parkinson's Disease Research Center of Excellence
- NIH/NINDS [NS40256, R01 NS057567, RC2 NS070276-01]
- Mayo Clinic Florida Research Committee CR programs
- Robert and Clarice Smith Fellowship
- Pacific Alzheimer Research Foundation [C06-01]
- German Research Foundation [LO 1555/3-1]
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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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