Genomic approaches to schizophrenia

Background: Genetic epidemiologic studies suggest that individual variation in susceptibility to schizophrenia is substantially genetic. However, like other common disorders, the mode of transmission is complex and probably reflects oligogenic inheritance against a polygenic background. Objective: The goal of this article was to introduce genomics as an approach to understanding the causes of schizophrenia. Conclusions: Genomic approaches to schizophrenia are becoming increasingly feasible as data from the Human Genome Project accumulate and technology improves. Attempts to identify genes for schizophrenia have been based on 4 main approaches: genetic linkage studies, studies of chromosomal abnormalities associated with the disorder, association studies, and convergent genomics. Several strong linkages have been found, and there is emerging consensus regarding at least some of the chromosomal regions likely to contain schizophrenia genes. However, moving from linked region to susceptibility gene is still difficult, given our poor understanding of the pathophysiology and population genetics, and the complexity of the phenotype. Despite this difficulty, positional candidate genes have been identified, and in 2 instances-neuregulin 1 and dysbindin-1-support has come from several studies. The rates of schizophrenia seen in individuals with deletions of chromosome 22q11, as well as linkage data, suggest that this chromosomal region might contain a susceptibility locus.