Schizophrenia Yields Some Genetic Secrets

"We looked at a relatively rare type of DNA change where people have a substantial portion of a chromosome either missing or extra. These are called copy number changes," Sklar explained.

In this case, the consortium found three deletions: one on chromosome 1 and two on chromosome 15, which were seen multiple times in people with schizophrenia. Two of the deletions had never been recognized before. "That triples the number of specific DNA areas that may be responsible for schizophrenia," Sklar said. "All of these together were found in about 1 percent of patients." But they conferred a very large risk, multiplying the odds of getting schizophrenia by a factor of more than 10, Stefansson said.

TheNature Geneticspaper identified three "single-nucleotide polymorphisms" (changes) or SNPs that were associated with schizophrenia and appear to be risk factors for the disease. The strongest association was with a variant near the gene ZNF804A, whose function may be to regulate other genes.

According to O'Donovan, other researchers have looked at what are called "whole chapters" in the genome. In contrast, his team honed in on what he described as tiny spelling differences.

The variations identified are much more common than those reported in the previous two papers.

"In addition to rare variants, we were able to convincingly show that common variants are involved in schizophrenia. But we don't know how much of a role they play compared with rare variants," O'Donovan said. "It means that virtually all of us have genes for schizophrenia, but probably those of us who don't have schizophrenia don't have enough of the genes or possibly have not been exposed to [an environmental stimulus]."

"Schizophrenia is the ultimate human disease, affecting the things that characterize us as individuals," Stefansson added. "Perhaps with a little bit of luck, we will gain insight into the pathogenesis of schizophrenia . . . and will discover enough of the variants to put together meaningful diagnostic instruments for this very difficult disease."

More information

There's more on schizophrenia at the U.S. National Institute of Mental Health.

SOURCES: July 29, 2008, teleconference with Pamela Sklar, M.D., Ph.D., director, genetics, Harvard Medical School; Kari Stefansson, M.D., CEO, deCODE, Reykjavik, Iceland; and Michael O'Donovan, Ph.D., professor, psychiatric genetics, Cardiff University, U.K.; July 30, 2008, online editions,NatureandNature Genetics