Replication in genome-wide association studies

Peter Kraft, Eleftheria Zeggini, John P.A. Ioannidis

Research output: Contribution to journalArticlepeer-review

220 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)561-573
Number of pages13
JournalStatistical Science
Volume24
Issue number4
DOIs
StatePublished - Nov 2009
Externally publishedYes

Keywords

  • Genome-wide association study
  • Metaanalysis
  • Replication

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