also often justified on the basis of initial findings that fail to hold up to the harsh light of replication. Imagine this hypothetical scenario: A researcher is interested in endophenotype X as an endophenotype for ADHD. Assume that two recent candidate gene studies have indicated that the COMT Val/Met polymorphism, which is thought to play an important role regulating dopamine availability in the prefrontal cortex (PFC), is related to ADHD. Our eager researcher conducts a candidate gene study of COMT in relation to endophenotype X, which turns out to yield a significant result: levels of endophenotype X are linearly related to the number of Val (Met) alleles. Excited about this result, s/he decides to conduct studies of other dopamine genes, some of which pan out whereas others do not. In the meantime, more studies examining the association between COMT and ADHD appear in the literature, many with negative results, and then a meta-analysis reports that there is no relationship between COMT and ADHD after all. Even worse, subsequent research indicates that the relationship between COMT and dopamine availability in PFC is weak. Now what does our researcher do? She has an interesting endophenotype finding based on a hypothesis that is
