Genetic epidemiology learned the importance of replication the hard way. Before the advent of genome-wide association (GWA) studies, most reported genotype-phenotype associations failed to replicate. There were a number of reasons for these conflicting results, including: inappropriate reliance on standard significance thresholds that did not take the low prior probability of association into account; small sample sizes; and failure to measure the same variant(s) across different studies.[2–4] In response, the field moved towards more stringent requirements for reporting associations, explicitly emphasizing replication.[5] Many high-profile journals now will not publish genotype-phenotype associations without concrete evidence of replication.[6]
