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Schizophrenia Linked to 8 Genetically Distinct Disorders

Update Date: Sep 15, 2014 12:36 PM EDT

New data suggest that schizophrenia, a chronic mental disorder characterized by difficulties differentiating between what is real and what is not, might not a single disease. Instead, the researchers concluded that schizophrenia could be the result of eight genetically distinct disorders that have their own unique symptoms.

For this study, the research team from Washington University School of Medicine set out to examine the potential genetic influences of the disease. The team analyzed DNA variations in 4,200 people diagnosed with schizophrenia and in 3,800 people without the mental disease that acted as the control group. The team matched the DNA variations in people with and without the disease to different symptoms that showed up in each individual patient. In total, they analyzed roughly 700,000 sites in a genome where one unit of DNA is changed, which is often called a single nucleotide polymorphism (SNP).

"Genes don't operate by themselves. They function in concert much like an orchestra, and to understand how they're working, you have to know not just who the members of the orchestra are but how they interact," C. Robert Cloninger, MD, PhD, one of the study's senior investigators, explained in the news release. "What we've done here, after a decade of frustration in the field of psychiatric genetics, is identify the way genes interact with each other, how the 'orchestra' is either harmonious and leads to health, or disorganized in ways that lead to distinct classes of schizophrenia."

The researchers found that how a group of genetic variations was clustered together determined people's risk of schizophrenia. For example, in patients experiencing hallucinations or delusions, their specific genetic variations interacted to create a 95 percent chance of having schizophrenia. In people with speech and behavioral symptoms, their genetic variations interacted to create a 100 percent risk of schizophrenia. Overall, the team identified 42 genetic variation clusters that increased people's risk of schizophrenia.

"In the past, scientists had been looking for associations between individual genes and schizophrenia," stated study co-investigator, Dragan Svrakic, PhD, MD, a professor of psychiatry at Washington University. "When one study would identify an association, no one else could replicate it. What was missing was the idea that these genes don't act independently. They work in concert to disrupt the brain's structure and function, and that results in the illness."

The study, "Uncovering the hidden risk architecture of the schizophrenias: Confirmation in three independent genome-wide association studies," was published in the American Journal of Psychiatry.

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