Similar independence approximations are made in GWA replication analyses, which check for close relationships among sampled individuals but otherwise treat separate studies of nonoverlapping samples as independent. A genealogical perspective suggests that replication studies are in fact pseudoreplication studies, owing to potential correlations among outcomes that could arise from shared genealogy. From this viewpoint, particularly in small populations, separate association studies identifying the same risk variant in a population might not provide the same degree of confirmation as replicate studies in a context in which events truly are independent121. As in the analysis of individual GWA studies, the independence assumption has provided a sensible initial strategy for replication studies, but unlike in the case of genealogical dependence within studies, approaches that account for dependence between studies have not yet been considered. The magnitude in real populations of the pseudoreplication effect — the degree to which separate association studies provide the same outcome as a result of shared ancestry of study participants — is unknown, so that it remains uncertain how likely a replication study is to detect a risk variant
