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Family studies suggest rare genetic mutations team up to cause schizophrenia
Date:5/28/2013

Using a novel method of analyzing genetic variations in families, researchers at Johns Hopkins have found that individually harmless genetic variations affecting related biochemical processes may team up to increase the risk of schizophrenia. They say their findings, reported May 28 in Translational Psychiatry, bring some clarity to the murky relationship between genetics and schizophrenia, and may lead to a genetic test that can predict which medications will be effective for individual patients.

"It's long been clear that schizophrenia runs in families, but schizophrenia as a simple inherited disease didn't make sense from an evolutionary point of view because people with the disease tend to have fewer children and the disease-causing genetic variants shouldn't survive," says Dimitri Avramopoulos, M.D., Ph.D., an associate professor of psychiatry in the McKusick-Nathans Institute of Genetic Medicine. Moreover, he says, studies searching for schizophrenia-linked gene variants have found only weak connections to a few genes nothing that would explain the persistent prevalence of the disease, which affects about 1 percent of the population.

Most geneticists believe that the culprit in so-called complex genetic diseases such as schizophrenia is not just one genetic variant, but more than one acting in concert. It's also likely that individual cases of the disease are caused by different combinations of variants, Avramopoulos says. He and fellow researchers took this hypothesis a step further, theorizing that while our bodies can usually compensate for one faulty gene that affects a particular system, more than one hit to the same system is likely to tip people toward disease.

The research team devised a technique for analyzing gene-sequencing data that explores whether variants cluster in a subset of cases in a non-random way. After finding support for their hypothesis in previously obtained data on 123 families with at least two s
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Contact: Shawna Williams
shawna@jhmi.edu
410-955-8236
Johns Hopkins Medicine
Source:Eurekalert

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