Schizophrenia has been revealed to be group of eight genetically distinct disorders as opposed to just one.
The new distinction could help improve diagnosis and treatment of the psychiatric illness, Washington University in St. Louis reported.
About 80 percent of the risk for schizophrenia is believed to be inherited, but scientists have been struggling to identify specific genes associated with the condition. A new approach allowed them to analyze genetic influences on more than 4,000 people with schizophrenia and identify distinct gene clusters that contribute to eight different classes of schizophrenia.
"Genes don't operate by themselves," said C. Robert Cloninger, MD, PhD, one of the study's senior investigators. "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."
The study matched precise DNA variations in people with and without schizophrenia to symptom in individual patients. The team analyzed y 700,000 sites within the genome in which a single unit of DNA is changed, called a single nucleotide polymorphism (SNP). They looked at SNPs in 4,200 people with schizophrenia and 3,800 healthy controls in order to learn how individual genetic variations interacted with each other and led to the illness.
"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," Cloninger said.
People with these genetic variations have between a 70 and 100 percent risk of developing some type of schizophrenia. The team identified 42 clusters of genetic variations that greatly increase the risk of schizophrenia.
"In the past, scientists had been looking for associations between individual genes and schizophrenia," said Dragan Svrakic, PhD, MD, a co-investigator and 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."
Once the researchers organized the genetic variations and the patients' symptoms they could see how specific clusters of DNA variations act together to cause a specific type of symptom. They found different symptom profiles could be grouped into eight distinctive disorders.
"People have been looking at genes to get a better handle on heart disease, hypertension and diabetes, and it's been a real disappointment," Cloninger said. "Most of the variability in the severity of disease has not been explained, but we were able to find that different sets of genetic variations were leading to distinct clinical syndromes. So I think this really could change the way people approach understanding the causes of complex diseases."
The findings were reported. Sept. 15 in The American Journal of Psychiatry.
