A welcome change in psychiatric genetics has been the widespread recognition of the essential role of uncompromising statistical rigor and replication. Put simply, the genome is a big place, and it is trivial to find false leads—non-significant but ‘suggestive’genomic findings that an integrative scientist might find ‘intriguing’. Indeed, due to advances in sequencing technology, the next few years are certain to see an explosion in observations of unique events in people with schizophrenia and other psychiatric disorders. Some of these will be claimed to be causal. However, the paucity of results from exome sequencing of sizable samples in autism 1–3 and schizophrenia, 4, 5 combined with the surprisingly high rates of deleterious exonic variation in apparently normal people, 6 indicates that it will be highly challenging to delineate disease-related variants from background noise. For example, even with the improbably optimistic assumption that 1% of schizophrenia cases are caused by fully penetrant mutations in one gene that has no confounding background variation, observing 10 deleterious mutations in 1000 cases and 0 in 1000 controls would not be clearly delineated from the distribution of test statistics across 15–20000 genes. In reality, locus heterogeneity, incomplete penetrance and realistic background variation will make this task markedly more difficult. As there is already an influential example of a unique genomic event, it is timely to review the genomics of ‘Disrupted in Schizophrenia 1’(DISC1), at (1; 11)(q42. 1; q14. 3) structural variant identified using cytogenetic methods. 7, 8 (The chromosomal bands are sometimes different from 1q42. 1 and 11q14. 3. I determined these bands by mapping the breakpoint sequences in Millar et al. 7. to hg19 using UCSC/BLAT.) Over 20 years after the initial report, the status of DISC1 as a risk factor for schizophrenia is unclear and perhaps polarized: some researchers are convinced that it is a proven etiological factor in schizophrenia, and others that it is not. Other groups await empirical data to resolve its role. Indeed, my group has found non-significant but ‘intriguing’results about DISC1 twice, and both times its potential salience faded with more data. 9, 10 The purpose of this editorial is to review the genetic evidence for the involvement of DISC1 in schizophrenia. There are important unanswered questions that need to be resolved for DISC1 to be established as a bona fide genetic risk factor for schizophrenia.