Meta-analysis of genetic association studies.

Meta-analysis, a statistical tool for combining results across studies, is becoming popular as a method for resolving discrepancies in genetic association studies. Persistent difficulties in obtaining robust, replicable results in genetic association studies are almost certainly because genetic effects are small, requiring studies with many thousands of subjects to be detected. In this article, we describe how meta-analysis works and consider whether it will solve the problem of underpowered studies or whether it is another affliction visited by statisticians on geneticists. We show that meta-analysis has been successful in revealing unexpected sources of heterogeneity, such as publication bias. If heterogeneity is adequately recognized and taken into account, meta-analysis can confirm the involvement of a genetic variant, but it is not a substitute for an adequately powered primary study.