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I.R. "OLYMPIAS"
Article . 2001
Data sources: I.R. "OLYMPIAS"
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Nature Genetics
Article . 2001 . Peer-reviewed
License: Springer TDM
Data sources: Crossref
Nature Genetics
Article . 2001
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Replication validity of genetic association studies

Authors: Ioannidis, J. P.; Ntzani, E. E.; Trikalinos, T. A.; Contopoulos-Ioannidis, D. G.;

Replication validity of genetic association studies

Abstract

The rapid growth of human genetics creates countless opportunities for studies of disease association. Given the number of potentially identifiable genetic markers and the multitude of clinical outcomes to which these may be linked, the testing and validation of statistical hypotheses in genetic epidemiology is a task of unprecedented scale. Meta-analysis provides a quantitative approach for combining the results of various studies on the same topic, and for estimating and explaining their diversity. Here, we have evaluated by meta-analysis 370 studies addressing 36 genetic associations for various outcomes of disease. We show that significant between-study heterogeneity (diversity) is frequent, and that the results of the first study correlate only modestly with subsequent research on the same association. The first study often suggests a stronger genetic effect than is found by subsequent studies. Both bias and genuine population diversity might explain why early association studies tend to overestimate the disease protection or predisposition conferred by a genetic polymorphism. We conclude that a systematic meta-analytic approach may assist in estimating population-wide effects of genetic risk factors in human disease.

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Greece
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Keywords

*Disease, Genetic Linkage/genetics, Genetic Markers/genetics, Genetic Markers, Polymorphism, Genetic, Genetic Linkage, Chromosome Mapping, Genetic Variation, Reproducibility of Results, Genetic Predisposition to Disease/*genetics, Genetic Variation/genetics, Bias, Meta-Analysis as Topic, Chromosome Mapping/*methods/statistics & numerical data, Bias (Epidemiology), Odds Ratio, Humans, Regression Analysis, Disease, Genetic Predisposition to Disease, Polymorphism, Genetic/genetics

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
2K
Top 0.1%
Top 0.01%
Top 0.1%
Green