Replication in Genome-Wide Association Studies

Details Replication in Genome-Wide Association Studies Replication in Genome-Wide Association Studies

2010-10-25

arxiv.org/abs/1010.5095v1

Statistical Science 2009, Vol. 24, No. 4, 561-573

Statistics

Methodology

Published in at http://dx.doi.org/10.1214/09-STS290 the Statistical Science (http://www.imstat.org/sts/) by the Institute of M

Scientific paper

10.1214/09-STS290

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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