July 31, 2008
UI team helps piece together genetic puzzle of schizophrenia
University of Iowa researchers contributed to a study that found a particular genetic variation is associated with schizophrenia. The severe mental health disorder affects nearly 1 percent of people in the United States and can include delusions, hallucinations and confused thinking.
The study, which was published online July 30 in the journal Nature Genetics, was led by Michael O'Donovan at Cardiff University in the United Kingdom. Also on July 30, two other research groups published separate findings in the journal Nature that identified genetic variations -- three deletions -- and confirmed a previously known deletion, all associated with schizophrenia.
Previous investigations have not involved such large sample sizes as the three new studies did, and taken together, they provide strong evidence that schizophrenia may result from interactions of large stretches of DNA on multiple locations in an individual's genome, said Donald W. Black, M.D., principal investigator for the UI site and professor of psychiatry at the UI Roy J. and Lucille A. Carver College of Medicine.
"The discoveries are meaningful because it has been difficult to link genes to mental illness with a great deal of confidence," Black said. "It's unlikely that one gene will explain the development of any mental illness, and in the case of schizophrenia, we strongly suspect that multiple genes are responsible for an increased vulnerability for the disorder."
The study involving the UI included DNA samples and thorough background information taken on 336 persons with schizophrenia at the UI site. Analysis of the samples identified variants at three loci on chromosome 2 as having strong independent risk factors for schizophrenia.
The strongest evidence for the variant was found near the gene ZNF804A, which encodes a protein that may act to regulate the expression of other genes. The association with that variant increased when individuals with bipolar disorder were included in the analysis, lending support to the notion that schizophrenia and bipolar disease share some risk factors.
"There are no genetic tests for schizophrenia, although that could change in the future," Black said. "However, genes are influenced by many factors, so having a gene that may be related to schizophrenia does not necessarily mean a person will develop the condition."
Black also noted that molecular genetics studies require hundreds, if not thousands, of cases so it is important for large groups of investigators to pool resources and knowledge.
"This study represent the fruition of nearly 10 years of work as I and other collaborators in the department have been involved in the Molecular Genetics of Schizophrenia Consortium," Black said.
"This paper helps show that molecular genetics work today is collaborative and international. It takes many years to collect cases, and the subsequent genetic analysis is not easy. The methods are constantly evolving. In fact, the methods used in this study were not the ones we originally proposed in the 1990s," he added.
The Molecular Genetics of Schizophrenia Consortium is funded by the National Institute of Mental Health, which is part of the National Institutes of Health. Black said the UI team hopes to pursue additional work on schizophrenia through the consortium. The Department of Psychiatry has been actively involved in the genetic research of mental disorders since the 1970s.
In addition to Black, UI researchers involved in the Nature Genetics paper were Raymond Crowe, M.D., professor emeritus of psychiatry, and Tom Wassink, M.D., associate professor of psychiatry.
NOTE TO EDITORS: This UI release includes information from a Nature/Nature Genetics news release.
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