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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Serval ID
serval:BIB_4C7B41911EAF
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Non-Replication of Association for Six Polymorphisms From Meta-Analysis of Genome-Wide Association Studies of Parkinson?s Disease: Large-Scale Collaborative Study
Journal
American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics
Author(s)
Evangelou E., Maraganore D.M., Annesi G., Brighina L., Brice A., Elbaz A., Ferrarese C., Hadjigeorgiou G.M., Krueger R., Lambert J.C., Lesage S., Markopoulou K., Mellick G.D., Meeus B., Pedersen N.L., Quattrone A., Van Broeckhoven C., Sharma M., Silburn P.A., Tan E.K., Wirdefeldt K., Ioannidis J.P.A.
Contributor(s)
Sutherland G.T., Siebert G.A., Theuns J., Crosiers D., Pickut B., Pals P., Engelborghs S., Nuytemans K., De Deyn P.P., Cras P., Agid Y., Bonnet A.M., Borg M., Brice A., Broussolle E., Damier P., Destée A., Dürr A., Durif F., Lesage S., Lohmann E., Pollak P., Rascol O., Tison F., Tranchant C., Viallet F., Vidailhet M., Tzourio C., Amouyel P., Loriot M.A., Gasser T., Riess O., Berg D., Schulte C., Klein C., Djarmati A., Lohmann K., Xiromerisiou G., Dardiotis E., Kountra P., Hattori N., Tomiyama H., Funayama M., Yoshino H., Li Y., Valente E.M., Ferraris A., Bentivoglio A.R., Ialongo T., Riva C., Corradi B., Opala G., Jasinska-Myga B., Klodowska-Duda G., Boczarska-Jedyna M., Belin A., Olson L., Galter D., Westerlund M., Sydow O., Nilsson C., Puschmann A., Maraganore D.M., Ahlskog J.E., de Andrade M., Lesnick T.G., Rocca W.A., Checkoway H.
ISSN
1552-4841 (Print)
1552-485X (Electronic)
ISSN-L
1552-4841
Publication state
Published
Issued date
2015
Peer-reviewed
Oui
Volume
0
Number
1
Pages
220-228
Language
english
Notes
Publication types: Article ; research-article Identifiant PubMed Central: PMC4699803
Abstract
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.
Keywords
Parkinson Disease/genetics
Pubmed
Web of science
Create date
25/07/2016 9:19
Last modification date
20/08/2019 15:00
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