Non-Replication of Association for Six Polymorphisms From Meta-Analysis of Genome-Wide Association Studies of Parkinson's Disease: Large-Scale Collaborative Study
Φόρτωση...
Ημερομηνία
Συγγραφείς
Evangelou, E.
Maraganore, D. M.
Annesi, G.
Brijhina, L.
Brice, A.
Elbaz, A.
Ferrarese, C.
Hadjigeorgiou, G. M.
Krueger, R.
Lambert, J. C.
Τίτλος Εφημερίδας
Περιοδικό ISSN
Τίτλος τόμου
Εκδότης
Περίληψη
Τύπος
Είδος δημοσίευσης σε συνέδριο
Είδος περιοδικού
peer reviewed
Είδος εκπαιδευτικού υλικού
Όνομα συνεδρίου
Όνομα περιοδικού
American Journal of Medical Genetics Part B-Neuropsychiatric Genetics
Όνομα βιβλίου
Σειρά βιβλίου
Έκδοση βιβλίου
Συμπληρωματικός/δευτερεύων τίτλος
Περιγραφή
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. (C) 2009 Wiley-Liss, Inc.
Περιγραφή
Λέξεις-κλειδιά
parkinson's disease, meta-analysis, genome-wide association, axon guidance, pathway, heterogeneity, uncertainty, challenges
Θεματική κατηγορία
Παραπομπή
Σύνδεσμος
<Go to ISI>://000273440500025
http://onlinelibrary.wiley.com/store/10.1002/ajmg.b.30980/asset/30980_ftp.pdf?v=1&t=h0xjyz6q&s=e1f6929e66071c6ac049da05e986542757beb8dd
http://onlinelibrary.wiley.com/store/10.1002/ajmg.b.30980/asset/30980_ftp.pdf?v=1&t=h0xjyz6q&s=e1f6929e66071c6ac049da05e986542757beb8dd
Γλώσσα
en
Εκδίδον τμήμα/τομέας
Όνομα επιβλέποντος
Εξεταστική επιτροπή
Γενική Περιγραφή / Σχόλια
Ίδρυμα και Σχολή/Τμήμα του υποβάλλοντος
Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών και Τεχνολογιών. Τμήμα Βιολογικών Εφαρμογών και Τεχνολογιών