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Genetic mapping triggers new hope on schizophrenia

Tuesday, July 22, 2014 | 6:00 a.m. CDT

WASHINGTON — Scientists have linked more than 100 spots in our DNA to the risk of developing schizophrenia, casting light on the mystery of what makes the disease tick.

Such work could eventually point to new treatments, although they are many years away. Already, the new results provide the first hard genetic evidence to bolster a theory connecting the immune system to the disease.

The study included the genetic codes of more than 150,000 people — nearly 37,000 of them diagnosed with the disease. Researchers found 108 genetic markers for risk of getting the disease, 83 of them not previously reported. And scientists say there are still likely more to be found.

"It's a genetic revelation; schizophrenia has been a mystery," said study co-author Steve McCarroll, director of genetics for the Broad Institute of MIT and Harvard. "Results like this give you things to work on. It takes it out of the zone of guesses about which genes are relevant."

The results were released Monday by the journal Nature. It takes large studies to ferret out genes related to schizophrenia risk because each gene generally has only a very weak effect.

Schizophrenia is a debilitating mental disorder that makes it hard to tell the difference between what is real and not real, and it affects about one out of every 100 people. Studies estimate that it costs $60 billion in the U.S. each year. Scientists have long known that genes play a part, and this work further confirms that.

The results are a "big step" toward finding drug therapies, said study lead author Michael O'Donovan, deputy director of the MRC Centre for Neuropsychiatric Genetics and Genomics at Cardiff University School of Medicine in Wales. While 108 genetic markers are a lot, the study authors say they tend to implicate a narrower group of biological functions, giving some but not too many hints for scientists to pursue.

"It's a map or maze. It's telling you where to start, it's not telling you where to end," O'Donovan said.

Scientists who didn't work on the study were excited by the possibilities it opens up.

"This makes me more optimistic than I was yesterday," said American Psychiatric Association President Thomas Summergrad, psychiatrist-in-chief at Tufts Medical Center.

Thomas Insel, director of the National Institute of Mental Health, which funded the work, said the study provides useful hints about the biology of the disease, especially the link to the immune system.

"This really is a big step forward," Insel said. "It's not an answer; it's a step forward toward an answer."

Scientists already knew that families with autoimmune disorders tend to have higher rates of schizophrenia, and there's been a link between certain viral infections in the second trimester of pregnancy and higher rates of schizophrenia in offspring, Insel said.

With the new work, "now it's very clear that there's something going in the immune system" with schizophrenia, said Eric Lander, founding director of the Broad Institute, which was heavily involved in the research.

O'Donovan figures most people have at least 20 to 30 genes that nudge them toward developing schizophrenia, probably many more, but don't have the disorder itself. That's because it may still take an environmental or emotional trigger to bring on the illness.

Insel was especially excited about one study finding: that people with the most genetic markers were 15 times more likely to have schizophrenia than those with the fewest markers. He said he hoped that scientists can eventually develop a genetic test to identify young people at high risk for the disease, so they can be offered early treatment.

But O'Donovan and McCarroll said the work is way too preliminary to even hint at that. Even the people with elevated risk of schizophrenia according to the test were far more likely to be free of the disorder than to have it.

As for developing treatments, "I don't want to pretend that anybody's going to make drugs easily," Lander said.

But he said the study of schizophrenia genetics is now to the point that "we can actually turn the lights on and see what's going on."


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