Genetics of schizophrenia.

Abstract: Genetic epidemiological studies suggest that individual variation in susceptibility to schizophrenia is largely genetic, but the mode of transmission is unknown. It is likely on theoretical and empirical grounds that risk in the population reflects both relatively common alleles with small effects and rare alleles with larger effects. Molecular genetic studies have identified several potential regions of linkage and two associated chromosomal abnormalities, and evidence is accumulating in favour of several positional candidate genes. Currently, the positional candidate genes for which we consider the evidence to be strong are those encoding dysbindin 1 (DTNBP1), neuregulin 1 (NRG1), and disrupted in schizophrenia 1 (DISC1). Recent advances in technology have made genome-wide association studies feasible. These have been used successfully to identify risk genes of small effect in many common diseases, and identification of risk genes for schizophrenia can be expected in the coming months. In addition, recent systematic searches for copy number variants (CNVs) in schizophrenia have provided evidence that sub-microscopic CNVs are over-represented in cases of schizophrenia. The identification of risk genes has already opened up new avenues for research aimed at understanding the pathogenesis of schizophrenia, and will continue to do so. It will also catalyse a re-appraisal of the classification of psychiatric disorders. [Copyright &y& Elsevier]