In a paper investigating the genetic basis for schizophrenia published in Nature in 1988, Sherrington et al. (1988) published what many thought was a breakthrough paper, wherein they concluded that they had found the “first strong evidence for the involvement of a single gene in the causation of schizophrenia.” Few would have thought then that in the ensuing three decades, and despite witnessing the human genome project completed, we still would know relatively little about how specific genes influence the development of schizophrenia and other psychiatric disorders. Moreover, what little we do know has no obvious public health significance. A major concern in the psychiatric literature has been that identifying genes is hamstrung by the inadequacy of the American Psychiatric Association's Diagnostic and Statistical Manuals (DSM) to carve nature at its joints with enough precision to facilitate success. The definition of DSM disorders depends little on biology; instead, they remain defined largely by consensus expert opinion, are obviously heterogeneous, and show substantial overlap. Against this backdrop, interest in strategies for gene finding that do not depend on the DSM has been high.
