  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.
