One must sift through a massive number of potential “hits” to decide which should be considered in subsequent stages of a multi-stage genotyping design, in independent replication studies, or in functional assays. This decision is usually based on statistical significance, but also entails expert judgment based on the internal consistency of the results and the coherence with other knowledge (e.g., the existence of other GWA associations for the same or related traits or biological pathways). Coherence has tended to be a more informal judgment, but various methods have emerged for formalizing this process. The following techniques can be viewed as well established and available for application now, although because of their novelty, there are few applications so far. See REF. 103 for an excellent review of the available techniques in the context of genetic main effects.
