The candidate gene strategy had a few notable successes in identifying genetic variation for other complex diseases. Influential examples included replicated associations of Alzheimer’s disease with common variation in APOE 5 and alcohol dependence with common variants in alcohol metabolic genes. 6 It was thus not unreasonable to hope that similar studies might work for schizophrenia. Realization of this expectation proved difficult. A pattern emerged whereby an initial claim of association for a seemingly plausible, even exciting, candidate gene for schizophrenia was followed by a mixed pattern of non-replications and replication. Thus, candidate gene association studies for schizophrenia became controversial. 7–10
