What have the genomics ever done for the psychoses?

Abstract

BackgroundDespite the substantial heritability of the psychoses and their genuine public health burden, the applicability of the genomic approach in psychiatry has been strongly questioned or prematurely dismissed.MethodA selective review of the recent literature on molecular genetic and genomic approaches to the psychoses including the early output from genome-wide association studies and the genomic analysis of DNA structural variation.ResultsSusceptibility variants at strong candidate genes have been identified including neuregulin, dysbindin, DISC1 and neurexin 1. Rare but highly penetrant copy number variants and new mutations affecting genes involved in neurodevelopment, cell signalling and synaptic function have been described showing some overlapping genetic architecture with other developmental disorders including autism. Thede-novomutations described offer an explanation for the familial sporadic divide and the persistence of schizophrenia in the population. The functional effects of risk variants at the level of cognition and connectivity has been described and recently, ZNF804A has been identified, and the MHC re-identified as risk loci, and it has been shown that at least a third of the variation in liability is due to multiple common risk variants of small effect with a substantial shared genetic liability between schizophrenia and bipolar affective disorder.ConclusionsThe genomics have done much for the psychoses to date and more is anticipated.