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Non-replication of ...
Non-replication of association for six polymorphisms from meta-analysis of genome-wide association studies of Parkinson's disease : large-scale collaborative study
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- Evangelou, Evangelos (author)
- University of Ioannina
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- Maraganore, Demetrius M. (author)
- Mayo Clinic Minnesota
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- Annesi, Grazia (author)
- CNR: National Research Council of Italy
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- Brighina, Laura (author)
- University of Milano-Bicocca
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- Brice, Alexis (author)
- Center For Immunology Of Viral Infections And Autoimmune Diseases
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- Elbaz, Alexis (author)
- Paris-Sorbonne University
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- Ferrarese, Carlo (author)
- University of Milano-Bicocca
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- Hadjigeorgiou, Georgios M. (author)
- University of Thessaly
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- Krueger, Rejko (author)
- University Hospital of Tubingen
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- Lambert, Jean-Charles (author)
- Lille 2 University
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Lesage, Suzanne (author)
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Markopoulou, Katerina (author)
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Mellick, George D. (author)
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Meeus, Bram (author)
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- Pedersen, Nancy L. (author)
- Karolinska Institutet
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Quattrone, Aldo (author)
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Van Broeckhoven, Christine (author)
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Sharma, Manu (author)
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Silburn, Peter A. (author)
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Tan, Eng-King (author)
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- Wirdefeldt, Karin (author)
- Karolinska Institutet
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Ioannidis, John P A (author)
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- Puschmann, Andreas (author)
- Lund University,Lunds universitet,Neurologi, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Neurology, Lund,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital
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(creator_code:org_t)
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- Wiley, 2010
- 2010
- English 9 s.
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In: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics. - : Wiley. - 1552-4841 .- 1552-485X. ; 153B:1, s. 8-220
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Abstract
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- Early genome-wide association (GWA) studies on Parkinson's disease (PD) have not been able to yield conclusive, replicable signals of association, perhaps due to limited sample size. We aimed to investigate whether association signals derived from the meta-analysis of the first two GWA investigations might be replicable in different populations. We examined six single-nucleotide polymorphisms (SNPs) (rs1000291, rs1865997, rs2241743, rs2282048, rs2313982, and rs3018626) that had reached nominal significance with at least two of three different strategies proposed in a previous analysis of the original GWA studies. Investigators from the "Genetic Epidemiology of Parkinson's Disease" (GEOPD) consortium were invited to join in this study. Ten teams contributed replication data from 3,458 PD cases and 3,719 controls. The data from the two previously published GWAs (599 PD cases, 592 controls and 443 sibling pairs) were considered as well. All data were synthesized using both fixed and random effects models. The summary allelic odds ratios were ranging from 0.97 to 1.09 by random effects, when all data were included. The summary estimates of the replication data sets (excluding the original GWA data) were very close to 1.00 (range 0.98-1.09) and none of the effects were nominally statistically significant. The replication data sets had significantly different results than the GWA data. Our data do not support evidence that any of these six SNPs reflect susceptibility markers for PD. Much stronger signals of statistical significance in GWA platforms are needed to have substantial chances of replication. Specifically in PD genetics, this would require much larger GWA studies and perhaps novel analytical techniques.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Keyword
- Genome-Wide Association Study
- Humans
- Parkinson Disease
- Polymorphism, Genetic
- Journal Article
- Meta-Analysis
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
Publication and Content Type
- art (subject category)
- ref (subject category)
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Evangelou, Evang ...
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Maraganore, Deme ...
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Annesi, Grazia
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Brighina, Laura
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Brice, Alexis
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Elbaz, Alexis
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show more...
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Ferrarese, Carlo
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Hadjigeorgiou, G ...
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Krueger, Rejko
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Lambert, Jean-Ch ...
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Lesage, Suzanne
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Markopoulou, Kat ...
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Mellick, George ...
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Meeus, Bram
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Pedersen, Nancy ...
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Quattrone, Aldo
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Van Broeckhoven, ...
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Sharma, Manu
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Silburn, Peter A ...
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Tan, Eng-King
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Wirdefeldt, Kari ...
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Ioannidis, John ...
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Puschmann, Andre ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
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American Journal ...
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Lund University
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Karolinska Institutet