Schizophrenia Yields Some Genetic Secrets

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"There has been precious little on diseases of the brain, and what seems to be emerging is that a lot of risk of brain diseases, including schizophrenia and autism, seems to be conferred by rare [gene] variants like rare deletions," said Dr. Kari Stefansson, senior author of one of the Nature papers and CEO of deCODE in Reykjavik, Iceland.

Schizophrenia tends to run in families, hence the focus on genetic determinants of the disease.

The first two papers, in Nature, compared the genomes of 3,300 individuals with schizophrenia against those of 3,200 individuals without the illness.

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"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.

The Nature Genetics paper 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.

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