Journal
NEUROBIOLOGY OF AGING
Volume 35, Issue 1, Pages -Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2013.07.013
Keywords
Parkinson's disease; LRRK2; SNCA; MAPT; Interaction; Genetics
Categories
Funding
- Michael J. Fox Foundation for Parkinson's Research
- Michael J. Fox Foundation for Parkinson's Research Edmond J. Safra Global Genetics Consortia program
- Morris K. Udall Center of Excellence in Parkinson's Disease Research [P50 NS072187]
- National Institutes of Health [R01 NS078086, R01ES10751]
- Canada Excellence Research Chairs program
- Province of British Columbia LifeLabs
- Genome BC,
- Italian Ministry of Health (Ricerca Corrente, Ricerca Finalizzata)
- Swedish Parkinson Academy
- Swedish Parkinson Foundation
- Federal Ministry for Education and Research (BMBF, NGFNplus) [01GS08134]
- NGFNplus (Neuron-Parkinson-subproject)
- CHRU de Lille, University of Lille 2, INSERM
- French Ministry PHRCs [1994/, 2002/1918, 2005/1914]
- Association France Parkinson
- Fondation de France [2004-013306]
- Fondation de la Recherche Medicale
- PPF
- Centre de Ressources Biologiques (IPL-Lille) and its scientific committee
- Centres de Ressources Biologiques (CHRU-Lille) and its scientific committee
- France-Parkinson Association
- program Investissement d'avenir [ANR-10-IAIHU-06]
- Swedish Research Council
- Swedish Society for Medical Research
- Swedish Society of Medicine
- Karolinska Institutet
- Parkinson Foundation in Sweden
- National Institute of Neurological Disorders and Stroke [1RC2NS070276, NS057567, P50NS072187]
- Mayo Clinic Florida Research Committee CR programs
- Geriatric Medical Foundation of Queensland
- Volkswagen Foundation
- Hermann and Lilly Schilling Foundation
- Research Committee of University of Thessaly [2845]
- Laboratory of Neurogenetics, Biomedicine Department, CERETETH, Larissa, Greece [01-04-207]
Ask authors/readers for more resources
The best validated susceptibility variants for Parkinson's disease are located in the alpha-synuclein (SNCA) and microtubule-associated protein tau (MAPT) genes. Recently, a protective p.N551K-R1398H-K1423K haplotype in the leucine-rich repeat kinase 2 (LRRK2) gene was identified, with p.R1398H appearing to be the most likely functional variant. To date, the consistency of the protective effect of LRRK2 p.R1398H across MAPT and SNCA variant genotypes has not been assessed. To address this, we examined 4 SNCA variants (rs181489, rs356219, rs11931074, and rs2583988), the MAPT H1-haplotype-defining variant rs1052553, and LRRK2 p.R1398H (rs7133914) in Caucasian (n = 10,322) and Asian (n = 2289) series. There was no evidence of an interaction of LRRK2 p.R1398H with MAPT or SNCA variants (all p >= 0.10); the protective effect of p.R1398H was observed at similar magnitude across MAPT and SNCA genotypes, and the risk effects of MAPT and SNCA variants were observed consistently for LRRK2 p.R1398H genotypes. Our results indicate that the association of LRRK2 p.R1398H with Parkinson's disease is independent of SNCA and MAPT variants, and vice versa, in Caucasian and Asian populations. (c) 2014 Elsevier Inc. All rights reserved.
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