Genetic associations in large versus small studies: an empirical assessment
Φόρτωση...
Ημερομηνία
Συγγραφείς
Ioannidis, J. P.
Trikalinos, T. A.
Ntzani, E. E.
Contopoulos-Ioannidis, D. G.
Τίτλος Εφημερίδας
Περιοδικό ISSN
Τίτλος τόμου
Εκδότης
Περίληψη
Τύπος
Είδος δημοσίευσης σε συνέδριο
Είδος περιοδικού
peer-reviewed
Είδος εκπαιδευτικού υλικού
Όνομα συνεδρίου
Όνομα περιοδικού
Lancet
Όνομα βιβλίου
Σειρά βιβλίου
Έκδοση βιβλίου
Συμπληρωματικός/δευτερεύων τίτλος
Περιγραφή
BACKGROUND: Advances in human genetics could help us to assess prognosis on an individual basis and to optimise the management of complex diseases. However, different studies on the same genetic association sometimes have discrepant results. Our aim was to assess how often large studies arrive at different conclusions than smaller studies, and whether this situation arises more frequently when findings of first published studies disagree with those of subsequent research. METHODS: We examined the results of 55 meta-analyses (579 study comparisons) of genetic associations and tested whether the magnitude of the genetic effect differs in large versus smaller studies. FINDINGS: We noted significant between-study heterogeneity in 26 (47%) meta-analyses. The magnitude of the genetic effect differed significantly in large versus smaller studies in ten (18%), 20 (36%), and 21 (38%) meta-analyses with tests of rank correlation, regression on SE, and regression on inverse of variance, respectively. The largest studies generally yielded more conservative results than the complete meta-analyses, which included all studies (p=0.005). In 14 (26%) meta-analyses the proposed association was significantly stronger in the first studies than in subsequent research. Only in nine (16%) meta-analyses was the genetic association significant and replicated without hints of heterogeneity or bias. There was little concordance in first versus subsequent discrepancies, and large versus small discrepancies. INTERPRETATION: Genuine heterogeneity and bias could affect the results of genetic association studies. Genetic risk factors for complex diseases should be assessed cautiously and, if possible, using large scale evidence.
Περιγραφή
Λέξεις-κλειδιά
Alleles, Clinical Trials as Topic/*methods, Genetic Markers, Humans, *Polymorphism, Genetic, *Sample Size
Θεματική κατηγορία
Παραπομπή
Σύνδεσμος
http://www.ncbi.nlm.nih.gov/pubmed/12598142
http://ac.els-cdn.com/S0140673603125160/1-s2.0-S0140673603125160-main.pdf?_tid=c2b44fbfac515285233af492116fb320&acdnat=1333364512_2a038b39b196f523af70509b473b4580
http://ac.els-cdn.com/S0140673603125160/1-s2.0-S0140673603125160-main.pdf?_tid=c2b44fbfac515285233af492116fb320&acdnat=1333364512_2a038b39b196f523af70509b473b4580
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