Curses--winner's and otherwise--in genetic epidemiology

Epidemiology. 2008 Sep;19(5):649-51; discussion 657-8. doi: 10.1097/EDE.0b013e318181b865.


The estimated effect of a marker allele from the initial study reporting the marker-allele association is often exaggerated relative to the estimated effect in follow-up studies (the "winner's curse" phenomenon). This is a particular concern for genome-wide association studies, where markers typically must pass very stringent significance thresholds to be selected for replication. A related problem is the overestimation of the predictive accuracy that occurs when the same data set is used to select a multilocus risk model from a wide range of possible models and then estimate the accuracy of the final model ("over-fitting"). Even in the absence of these quantitative biases, researchers can over-state the qualitative importance of their findings--for example, by focusing on relative risks in a context where sensitivity and specificity may be more appropriate measures. Epidemiologists need to be aware of these potential problems: as authors, to avoid or minimize them, and as readers, to detect them.

Publication types

  • Comment
  • Review

MeSH terms

  • Alleles
  • Epidemiologic Research Design*
  • Genetic Research*
  • Genetic Variation*
  • Genome, Human
  • Humans
  • Linkage Disequilibrium*