Lack of replication of thirteen single-nucleotide polymorphisms implicated in Parkinson's disease: a large-scale international study
| Autor: | Carlo Ferrarese, Lorene M. Nelson, Caroline M. Tanner, Brian K. Fiske, George D. Mellick, Richard M. Myers, Beate Ritz, Grazia Annesi, Karin Wirdefeldt, Christine Van Broeckhoven, Karen Marder, Marie Dehem, Stewart A. Factor, Donald S. Higgins, John G. Nutt, Stephen K. Van Den Eeden, Andrea Carmine Belin, Cyrus P. Zabetian, Rejko Krüger, Haydeh Payami, Jennifer S. Montimurro, Georgios M. Hadjigeorgiou, John P. A. Ioannidis, Hideshi Kawakami, Audrey Southwick, Ali Samii, Alexis Elbaz, Richard Mayeux, Thomas A Trikalinos |
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| Přispěvatelé: | Neuroépidémiologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Division of Epidemiology, Department of Health Research and Policy, Stanford University, New York State Department of Health [Albany], Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, The Michael J Fox Foundation for Parkinson's Research, Institute of Neurological Sciences, National Research Council [Italy] (CNR), Neuroscience Department, Karolinska Institutet [Stockholm], Department of Neurology, Emory University [Atlanta, GA], Department of Neuroscience-Section of Neurology, Università degli Studi di Milano-Bicocca [Milano] (UNIMIB), School of Medicine, Larissa, University of Thessaly [Volos] (UTH), Parkinson's Disease and Movement Disorder Clinic, Albany Medical College, Department of Epidemiology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Center of Neurology and Hertie-Institute for Clinical Brain Research, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, The Gertrude H Sergivesky Center, Columbia University College of Physicians and Surgeons, Eskitis Institute for Cell and Molecular Therapies, Griffi th University, Oregon Health and Science University [Portland] (OHSU), Department of Epidemiology, University of California [Los Angeles] (UCLA), University of California-University of California, Parkinson Disease Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, The Parkinson's Institute, The Parkinson's Institute, Sunnyvale, Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, Antwerpen, Division of Research, Kaiser Permanente, Department of Medical Epidemiology and Biostatistics (MEB), Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, University of Washington [Seattle], Genoscreen, Genoscreen, Lille, Department of Genetics [Stanford], Stanford Medicine, Stanford University-Stanford University, Theuns, Jessie, Pals, Philippe, Nuytemans, Karen, Pickut, Barbara, Cras, Patrick, De Deyn, Peter Paul, Tzourio, Christophe, University of Ioannina, Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), University of California (UC)-University of California (UC), Elbaz, A, Nelson, L, Payami, H, Ioannidis, J, Fiske, B, Annesi, G, Carmine Belin, A, Factor, S, Ferrarese, C, Hadjigeorgiou, G, Higgins, D, Kawakami, H, Krueger, R, Marder, K, Mayeux, R, Mellick, G, Nutt, J, Ritz, B, Samii, A, Tanner, C, van Broeckhoven, C, van den Eeden, S, Wirdefeldt, K, Zabetian, C, Dehem, M, Montimurro, J, Southwick, A, Myers, R, Trikalinos, T |
| Jazyk: | angličtina |
| Rok vydání: | 2006 |
| Předmět: |
Male
Linkage disequilibrium Polymorphism Single Nucleotide/*genetics Ethnic origin Linkage Disequilibrium 0302 clinical medicine Odds Ratio Genetics MESH: Aged 0303 health sciences MESH: Middle Aged MESH: Polymorphism Single Nucleotide MESH: Genetic Predisposition to Disease Middle Aged MESH: Confidence Intervals 3. Good health MESH: Linkage Disequilibrium Meta-analysis Female [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] MESH: Meta-Analysis Single-nucleotide polymorphism Biology Article Parkinson Disease/epidemiology/*genetics 03 medical and health sciences Meta-Analysis as Topic Genetic predisposition Confidence Intervals SNP Humans [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] 030304 developmental biology Aged MED/26 - NEUROLOGIA MESH: Humans Genetic heterogeneity International Cooperation Odds ratio MESH: Odds Ratio MESH: Male MESH: International Cooperation Genetic Predisposition to Disease [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie Parkinson's disease single-nucleoide polymorphism [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie Neurology (clinical) MESH: Female 030217 neurology & neurosurgery MESH: Parkinson Disease |
| Zdroj: | The Lancet Neurology The Lancet Neurology, Elsevier, 2006, 5 (11), pp.917-23. ⟨10.1016/S1474-4422(06)70579-8⟩ The lancet neurology The Lancet Neurology, 2006, 5 (11), pp.917-23. ⟨10.1016/S1474-4422(06)70579-8⟩ |
| ISSN: | 1474-4422 1474-4465 |
| DOI: | 10.1016/S1474-4422(06)70579-8⟩ |
| Popis: | International audience; BACKGROUND: A genome-wide association study identified 13 single-nucleotide polymorphisms (SNPs) significantly associated with Parkinson's disease. Small-scale replication studies were largely non-confirmatory, but a meta-analysis that included data from the original study could not exclude all SNP associations, leaving relevance of several markers uncertain. METHODS: Investigators from three Michael J Fox Foundation for Parkinson's Research-funded genetics consortia-comprising 14 teams-contributed DNA samples from 5526 patients with Parkinson's disease and 6682 controls, which were genotyped for the 13 SNPs. Most (88%) participants were of white, non-Hispanic descent. We assessed log-additive genetic effects using fixed and random effects models stratified by team and ethnic origin, and tested for heterogeneity across strata. A meta-analysis was undertaken that incorporated data from the original genome-wide study as well as subsequent replication studies. FINDINGS: In fixed and random-effects models no associations with any of the 13 SNPs were identified (odds ratios 0.89 to 1.09). Heterogeneity between studies and between ethnic groups was low for all SNPs. Subgroup analyses by age at study entry, ethnic origin, sex, and family history did not show any consistent associations. In our meta-analysis, no SNP showed significant association (summary odds ratios 0.95 to 1.08); there was little heterogeneity except for SNP rs7520966. INTERPRETATION: Our results do not lend support to the finding that the 13 SNPs reported in the original genome-wide association study are genetic susceptibility factors for Parkinson's disease. |
| Databáze: | OpenAIRE |
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