Replication in genome-wide association studies.
paper
Cited
Public
- Authors
- Kraft, Peter; Zeggini, Eleftheria; Ioannidis, John P A
- Year
- 2009
- Journal
- Statistical science : a review journal of the Institute of Mathematical Statistics
- PMID
- 20454541
- DOI
- 10.1214/09-STS290
- PMCID
- PMC2865141
Replication helps ensure that a genotype-phenotype association observed in a genome-wide association (GWA) study represents a credible association and is not a chance finding or an artifact due to uncontrolled biases. We discuss prerequisites for exact replication; issues of heterogeneity; advantages and disadvantages of different methods of data synthesis across multiple studies; frequentist vs. Bayesian inferences for replication; and challenges that arise from multi-team collaborations. While consistent replication can greatly improve the credibility of a genotype-phenotype association, it may not eliminate spurious associations due to biases shared by many studies. Conversely, lack of replication in well-powered follow-up studies usually invalidates the initially proposed association, although occasionally it may point to differences in linkage disequilibrium or effect modifiers across studies.
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