The Think Tank discussion covered possible considerations for addressing challenges in replication. One suggestion was to incorporate supporting biological knowledge, noting that functional studies may serve as independent support of a true association when an appropriate independent replication population is not present. However, the best approach for such incorporation is not clear, and participants stressed the importance of strong communication between the investigators performing the initial GEWIS, and those performing biological assays for follow-up. The need for independent replication in a second population versus performing biological assays must be balanced against cost of follow-up. Another possibility is to focus on environmental exposures with known replication datasets available. These replication-ready data sets could include cohorts with pre-diagnostic data and stored biospecimens; and existing data could be leveraged through enhanced data sharing. Sharing of null results through a clearinghouse, as discussed above, 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
