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
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
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