Some bias-adjusted estimates were still more extreme than the estimates from the independent replication studies. In those instances, the selection adjusted CIs typically excluded the null hypotheses value when the SNPs failed to replicate. Residual difference between bias-corrected ORs and replication ORs may be due to the ascertainment differences between the initial sample and the replication sample or to the approximation we chose for the p-value selection used to choose SNPs for further evaluation, in some of the studies examined. For example, the initial sample might be genetically ‘enriched’ by including cases with a family history of the study disease to increase statistical power. These enriched genetic cases may have a comparatively more extreme ORs compared to those from populations used for subsequent replication studies.
