Molecular Genetics of Schizophrenia

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Schizophrenia is a severe psychiatric disorder, which affects approximately 1% of the population. It is characterised by so-called psychotic symptoms, in particular delusions (false beliefs) and hallucinations (false perceptions), the latter being often in the form of hearing voices. Sufferers also tend to show altered emotional reactivity, impairments of thinking and reasoning and bizarre behaviour. Signs can be present from early childhood, but usually the disorder has its clinically detectable onset in the late teens and early 20?s. This age of onset, combined with the facts that many patients respond poorly or even not at all to any form of treatment, and for those that do respond, relapse is usually frequent, mean that the illness typically impacts on the vast majority of an individual?s adult life. This makes schizophrenia a major burden on the patient, their family and wider society. It has been clear for a century that schizophrenia runs in families, and this is now known to be largely due to genes rather than the family environment. Schizophrenia is clearly a brain disease but in spite of much research, it has not been possible to identify specific brain abnormalities that cause the disorder. Such knowledge is likely to be required for the development of truly effective treatments. It is our belief that the best hope of identifying the abnormalities that underlie schizophrenia is to identify the nature of the genetic susceptibility. This has proven difficult because schizophrenia, like other common diseases, does not occur as a result of a single genetic mutation, but reflects the operation of a large number of ?risk genes? each of which is responsible for only a small increase in risk of the disorder. It is really the combination of genes inherited at birth that determine someone?s risk. Modern genetic methods are, for the first time, allowing the great majority of variation in a person?s DNA to be assessed in a single experiment. If this technology is applied to a sufficiently large number of people, it is possible to identify risk genes that cause even fairly small increases in risk for a disease. This approach has been successfully applied to other common diseases such as asthma, diabetes, heart disease etc. We are proposing to use similar methods in large samples of patients that we and our collaborators have assembled over many years, precisely with a view to undertaking these studies.