Advances in the genetics of schizophrenia: will high-risk copy number variants be useful in clinical genetics or diagnostics?

Schizophrenia is a highly heritable, common mental illness, affecting 1% of the population worldwide. It is currently diagnosed using exclusive clinical criteria, and at present there are no genetic tests to facilitate this process. There are also no reliable means to predict who will develop the disease in later life. Genetic counselling uses crude estimates of risk based on family history, as the strongest predictive factor is having an affected first-degree relative. It has recently become apparent that large de novo deletions in the genome (copy number variants, or CNVs) can increase risk of the disease by tenfold or more. The purpose of this report is to assess whether these ‘high risk’ pathogenic CNVs might be useful in a clinical genetic or diagnostic setting. Routine use of laboratory techniques such as comparative genome hybridisation will reveal these de novo CNVs in standard investigative procedures for referrals to clinical genetics. The lack of disease specificity of CNVs presents problems for their use in diagnosis at present. Currently, there is also insufficient evidence in relation to schizophrenia to suggest that clear clinical benefit would be gained from learning one's genetic status pre-symptomatically. However, this is likely to change rapidly in the near future as knowledge of the genetic and environmental basis of schizophrenia accrues and increasingly effective measures for early intervention and risk reduction are developed.