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Genes Provide Clue For Schizophrenia Risk

6 July 2009
Appeared in BioNews 515

Thousands of tiny genetic variations that could collectively be responsible for more than a third of the inherited risk of schizophrenia have been identified for the first time. Data was pooled from three separate studies and reanalysed to uncover the results. Further, a common genetic basis was found for schizophrenia and bipolar disorder, which have previously been considered as separate conditions. The three linked papers describing the research were published together online in the journal Nature, and the hope is that the findings could lead to new diagnostic tests and treatments for the millions affected worldwide.

Schizophrenia is a chronic, long-term mental illness that appears in late adolescence, or early adulthood, and can result in hallucinations, depression, paranoia and persistent delusions. It affects roughly one per cent of the world's population at some time in their life. Bipolar disorder, also known as manic depression, is characterised by abnormal shifts in mood, energy and activity levels, essentially exaggerating the 'ups and downs' that we all experience, often resulting in an increased risk of suicide. Collectively these conditions affect up to one in 50 Britons and are estimated to cost the NHS £2bn a year.

Between them, the International Schizophrenia Consortium, the Molecular Genetics of Schizophrenia consortium and SGENE analysed genetic data from 8,014 people with schizophrenia and compared them to samples from 19,090 people who did not have the condition. The largest genetic differences between study participants with and without schizophrenia were found on a stretch of chromosome 6 called 'the Major Histocompatibility Complex'. This area contains numerous genes associated with immune response, raising the possibility that immune function plays a role in schizophrenia. The researchers believe this might help explain why environmental factors seem to affect risk for schizophrenia - for example, there is some evidence that children whose mothers contract flu while pregnant have a higher risk.

However, the cause of schizophrenia remains unclear, even although it is estimated that 80-90 per cent of cases are inherited. The problem lies in the fact that most cases are believed to be caused by complex interactions among a large number of genes, with any one gene variant contributing only a small amount to a person's risk. In this latest research, some 30,000 such genetic variants were found to be more common in people with schizophrenia, and a similar pattern was found in people with bipolar disorder indicating a previously unidentified overlap between the two conditions.

Thomas Insel, director of the US National Institute for Mental Health in Bethesda, Maryland (which part-funded the studies), said: 'If some of the same genetic risks underlie schizophrenia and bipolar disorder, perhaps these disorders originate from some common vulnerability in brain development. Of course the big question then is how some people develop schizophrenia and others develop bipolar disorder.'

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