Bayesian meta-analysis and meta-regression for gene-disease associations and deviations from Hardy-Weinberg equilibrium
Φόρτωση...
Ημερομηνία
Συγγραφείς
Salanti, G.
Higgins, J. P.
Trikalinos, T. A.
Ioannidis, J. P.
Τίτλος Εφημερίδας
Περιοδικό ISSN
Τίτλος τόμου
Εκδότης
Περίληψη
Τύπος
Είδος δημοσίευσης σε συνέδριο
Είδος περιοδικού
peer-reviewed
Είδος εκπαιδευτικού υλικού
Όνομα συνεδρίου
Όνομα περιοδικού
Stat Med
Όνομα βιβλίου
Σειρά βιβλίου
Έκδοση βιβλίου
Συμπληρωματικός/δευτερεύων τίτλος
Περιγραφή
Violation of Hardy-Weinberg equilibrium (HWE) can raise doubts about the validity of the conclusions from genetic association studies. However, for most currently performed gene-disease association studies, the available tests have low power to detect deviations from HWE. We consider this issue from a meta-analysis perspective, and suggest an approach to estimate the deviation and investigate its relationship with the observed genetic effects. Different degrees of deviation from HWE have previously been proposed as a potential source of heterogeneity across studies. We present a hierarchical meta-regression model that can be applied to test this assumption, using the concept of the fixation coefficient. We re-analyse seven meta-analyses to illustrate these methods. The uncertainty in the genetic effect estimate tended to increase once the fixation coefficient was taken into account. Dependence of the genetic effect size on the deviation from HWE was found in one meta-analysis, while in the other six examples, deviations from HWE did not clearly explain between-study heterogeneity in the genetic effects. The proposed hierarchical models allow the synthesis of data across gene-disease association studies with appropriate consideration of HWE issues.
Περιγραφή
Λέξεις-κλειδιά
Alleles, *Bayes Theorem, Case-Control Studies, Genetic Markers, Humans, *Meta-Analysis as Topic, *Models, Genetic, *Regression Analysis
Θεματική κατηγορία
Παραπομπή
Σύνδεσμος
http://www.ncbi.nlm.nih.gov/pubmed/16685693
http://onlinelibrary.wiley.com/store/10.1002/sim.2575/asset/2575_ftp.pdf?v=1&t=h0dojue5&s=dcbc1256ef21511a4f86f9576b7d1623c895375d
http://onlinelibrary.wiley.com/store/10.1002/sim.2575/asset/2575_ftp.pdf?v=1&t=h0dojue5&s=dcbc1256ef21511a4f86f9576b7d1623c895375d
Γλώσσα
en
Εκδίδον τμήμα/τομέας
Όνομα επιβλέποντος
Εξεταστική επιτροπή
Γενική Περιγραφή / Σχόλια
Ίδρυμα και Σχολή/Τμήμα του υποβάλλοντος
Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής