would foster replication of both positive and negative findings. A final consideration relates to the population size for the initial observation. When performing well-designed studies of suitably large samples sizes (50–100K individuals) from multiple studies, observing an interaction provides stronger credibility and therefore, the requirement for independent replication may be lessened. However, heterogeneity across the component studies may provide insights about effect modifiers or may provide evidence that the SNP found to be interacting with the environmental exposure is a marker and not the directly causative SNP.
