Hints about schizophrenia emerge from genetic study

Dozens of DNA changes may underlie troubling mental disorder

By combing through the genomes of over 30,000 people with schizophrenia, scientists have found more than 100 stretches of DNA that may raise a person’s risk of the disorder. Although it’s the largest genetic investigation of a psychiatric disorder, the study provides only clues to the disease’s origins — not answers.

The mega-analysis, published July 22 in Nature, is an important and necessary step toward developing new treatments for schizophrenia, says study coauthor Michael O’Donovan, a psychiatrist at the Cardiff University School of Medicine in Wales. But the heart of the disorder is still a mystery. “People shouldn’t be phoning up their doctors tomorrow and saying, ‘What’s this stuff done for treatment?’ That’s going to take years to filter through,” he says.

About 1 percent of Americans have schizophrenia, a disorder marked by hallucinations, paranoia and dysfunctional ways of thinking. Although the disease often runs in families, doctors and researchers have struggled to pinpoint the genes involved. The new study provides the most comprehensive identification yet of potential genetic culprits. Ultimately the identified DNA regions might reveal a deeper understanding of how the disease begins and progresses — and how to treat it. 

“For the first time, we can start to see the underlying biological basis of the disease, and to lay the foundation for understanding this disorder and eventually developing treatments,” Eric Lander, director of the Broad Institute of MIT and Harvard, one of the research centers involved in the study, said in a webcast announcement of the results.

O’Donovan worked with a large international team of scientists that collected DNA samples from people with schizophrenia from around the world, as well as samples that had been analyzed in earlier studies. As part of a genome-wide association study, or GWAS, the researchers compared DNA from people with schizophrenia with DNA from over 45,000 people without the disorder. One or several variations in the DNA’s chemical components cropped up in 108 distinct genome locales, the team found.

Several of these hot spots had been identified in earlier schizophrenia genome-wide studies (SN: 8/1/09, p. 10). The new study found an additional 83 spots in the genome. “There are just loads and loads of genes” involved with schizophrenia, O’Donovan says. “We’re still mining the biology of it.”

Certain finds made sense: One region includes the genetic blueprint for a protein called dopamine receptor D2, thought to be the target of some psychiatric drugs. Other areas include genes for proteins involved with the brain chemical glutamate, a neurotransmitter that has aroused suspicion of having a role in schizophrenia. Affected areas also include genes that are active in immune cells, suggesting a link between the immune system and schizophrenia.

“There is a whole pile of genes there that have never been on anyone’s list before,” says psychiatrist Jonathan Flint of the University of Oxford, who wasn’t involved in the study. That genetic bounty is “a great step forward,” he says.  

A person’s risk of schizophrenia increases just slightly, around 0.1 percent, when the individual has particular changes in one of the genetic regions identified in the study, O’Donovan says. That means that the stretches of DNA identified in this new research won’t be able to predict who will develop schizophrenia.

Many spots in the genome that contribute to schizophrenia remain undiscovered. By some estimates, hundreds or even thousands more genome locations could be involved. O’Donovan and his colleagues plan on conducting even larger studies in the next year or so that may reveal some of these hidden spots.

Laura Sanders is the neuroscience writer. She holds a Ph.D. in molecular biology from the University of Southern California.

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