Replication of MAPT and SNCA,but not PARK16‐18, as susceptibility genes for Parkinson's disease |
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| Authors: | Ignacio F. Mata PhD Dora Yearout BS Victoria Alvarez PhD Eliecer Coto PhD Lorena de Mena BS Renee Ribacoba MD Oswaldo Lorenzo‐Betancor MD Lluis Samaranch PhD Pau Pastor MD PhD Sebastian Cervantes MD Jon Infante MD Ines Garcia‐Gorostiaga MD Maria Sierra MD Onofre Combarros MD Katherine W. Snapinn MS Karen L. Edwards PhD Cyrus P. Zabetian MD MS |
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| Affiliation: | 1. Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA;2. Department of Neurology, University of Washington School of Medicine, Seattle, Washington, USA;3. Laboratorio de Genetica Molecular, Instituto de Investigacion Nefrologica (IRSINFRIAT), Hospital Universitario Central de Asturias, Oviedo, Spain;4. Neurology Department, Hospital Alvarez‐Buylla, Mieres, Spain;5. Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research, University of Navarra, Pamplona, Spain;6. Department of Neurology, Clínica Universidad de Navarra, University of Navarra School of Medicine, Pamplona, Spain;7. CIBERNED, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, Spain;8. Department of Neurology and Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), “Marques de Valdecilla” University Hospital, Santander, Spain;9. Neurology Service, Hospital de Galdakao, Vizcaya, Spain;10. Department of Epidemiology, University of Washington, Seattle, Washington, USA |
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| Abstract: | Recent genome‐wide association studies of Parkinson's disease have nominated 3 new susceptibility loci (PARK16‐18) and confirmed 2 known risk genes (MAPT and SNCA) in populations of European ancestry. We sought to replicate these findings. We genotyped single‐nucleotide polymorphisms in each of these genes/loci in 1445 Parkinson's disease patients and 1161 controls from northern Spain. Logistic regression was used to test for association between genotype and Parkinson's disease under an additive model, adjusting for sex, age, and site. We also performed analyses stratified by age at onset. Single‐nucleotide polymorphisms in MAPT (rs1800547; P = 3.1 × 10?4) and SNCA (rs356219; P = 5.5 × 10?4) were significantly associated with Parkinson's disease. However, none of the markers in PARK16‐18 associated with Parkinson's disease in the overall sample, or in any age stratum, with P values ranging from .09 to .88. Although our data further validate MAPT and SNCA as Parkinson's disease susceptibility genes, we failed to replicate PARK16, PARK17, and PARK18. Potential reasons for the discordance between our study and previous genome‐wide association studies include effects of population structure, power, and population‐specific environmental interactions. Our findings suggest that additional studies of PARK16‐18 are necessary to establish the role of these loci in modifying risk for Parkinson's disease in European‐derived populations. © 2011 Movement Disorder Society |
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| Keywords: | Parkinson's disease genome‐wide replication |
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