The discoveries, reported online in the journal Nature yesterday, stem from a mammoth effort to scan the genomes of more than 3,000 schizophrenia patients, the most extensive search for abnormalities published to date. Scientists said the work represents a significant step toward revealing the genetic roots of a devastating disease that has long stymied them.
"These papers represent the first rock-solid foundation knowledge of what can cause schizophrenia," said Michael O'Donovan, a professor at Cardiff University in Wales and lead author of a related paper in the journal Nature Genetics.
Taken together, the three hot spots are uncommon, accounting for only about 1 percent of schizophrenia cases. But the findings may point the way toward many more such genetic glitches that explain many more cases, researchers say.
The findings are "the tip of the iceberg," said Deborah Levy, a researcher in schizophrenia genetics at McLean Hospital in Belmont who was not involved in the studies. "They reveal an entirely unsuspected genetic mechanism responsible for a substantial proportion of schizophrenia. They also indicate that oftentimes, these genetic events occur spontaneously rather than being inherited."
Schizophrenia, which affects at least 2 million Americans, has long posed a major mystery. It clearly involves a strong genetic element, often running in families. And its prevalence in the population tends to remain steady over time, at about 1 percent. Yet people with schizophrenia usually start having symptoms - hallucinations, thinking problems, and more - in young adulthood, so many do not end up having children. So how does it remain so common in successive generations?
Two theories currently prevail. One suggests that families may pass along common genes that contribute to schizophrenia, but for various reasons, in most members, those genes do not combine to produce the disease.
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