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Many Genetic Contributions To Schizophrenia, Bipolar Disorder Discovered

Date:
July 2, 2009
Source:
Massachusetts General Hospital
Summary:
Scientists have discovered that many common genetic variants contribute to a person's risk of schizophrenia, providing the first molecular evidence that this form of genetic variation is involved in schizophrenia. The researchers also found that many of these DNA variations also are involved in bipolar disorder but not in several nonpsychiatric diseases.

Schizophrenia and bipolar disorder share genetic roots that appear to be specific to serious mental disorders, and are not shared by non-psychiatric illnesses. Bars representing different study samples show that the same genetic variations that account for risk in both mental disorders account for virtually none of the risk for coronary artery disease, Crohn's disease, hypertension, rheumatoid arthritis, or Type 1 or Type 2 diabetes.
Credit: Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Harvard University.

An international research consortium has discovered that many common genetic variants contribute to a person's risk of schizophrenia and explain at least a third of the risk of inheriting the disease, providing the first molecular evidence that this form of genetic variation is involved in schizophrenia. The researchers also found that many of these DNA variations also are involved in bipolar disorder but not in several non-psychiatric diseases.

The findings, reported by the International Schizophrenia Consortium and published online in the journal Nature, represent a new way of thinking about the genetics of psychiatric diseases, which seem to involve not only rare variants but also a significant number of common ones as well.

"While our study finds a surprising number of genetic effects, we fully expect that future work will assemble them into meaningful pathways that will teach us about the biology of schizophrenia and bipolar disorder," says Pamela Sklar, MD, PhD, of the Massachusetts General Hospital (MGH) Department of Psychiatry and Center for Human Genetic Research (CHGR), a senior associate member of the Broad Institute of MIT and Harvard and corresponding author of the Nature paper.

Co-corresponding author Shaun Purcell, PhD – also of MGH Psychiatry and the CHGR, and an associate member of the Broad Institute – emphasizes that "how these genetic variants translate into schizophrenia or bipolar disorder for a given patient is not yet known." Sklar and Purcell stress that, although these results are remarkably robust and give insight into the underlying genetics of these diseases, they cannot currently be used as a diagnostic test or to predict an individual's personal risk.

Schizophrenia is a common and often devastating brain disorder characterized by persistent delusions and hallucinations. It affects about 1 percent of the world's population and usually strikes in late adolescence or early adulthood. Despite the availability of treatments, the course of the illness is usually chronic, and response to treatments is often incomplete, leading to prolonged disability and personal suffering. Family history, which reflects genetic inheritance, is a strong risk factor for both schizophrenia and bipolar disorder, and it has generally been assumed that dozens of genes, along with environmental factors, contribute to disease risk.

Formed in 2006, the International Schizophrenia Consortium is led by senior researchers from 11 institutes in Europe and the USA. Major funding and resources for the current work were provided by the Broad Institute's Stanley Center for Psychiatric Research. Equally crucial to the success of the project was the willingness of consortium groups to share thousands of patient DNA samples collected over many years.

In the current study, the researchers tested hundreds of thousands of genetic variants (single nucleotide polymorphisms) in more than 3,300 individuals with schizophrenia and 3,600 individuals without the disorder. The work used novel analytical techniques based on theoretical models developed by consortium members Naomi Wray, PhD, and Peter Visscher, PhD, of the Queensland Institute of Medical Research, Brisbane, Australia.

The most critical – and surprising – finding was that the same large group of genetic variants was more common in all groups of schizophrenia patients, even though the DNA samples were collected by different investigators and tested in different laboratories. The additional discovery that these schizophrenia-related variants were also common in people with bipolar disorder was particularly striking, since the two disorders are considered to be distinct, although related, conditions.

"The consortium has taken important steps towards unearthing the complex genomic architecture of schizophrenia and other psychotic disorders, and this paper is another example of that critical work," said Edward Scolnick, MD, director of the Stanley Center for Psychiatric Research at the Broad Institute. "To fulfill the promise of these early studies, we as a community will need to continue to fully define the genetic basis of these disorders and ensure that our insights help improve the diagnostic and therapeutic options for patients and their families."

Thomas Insel, MD, director of the National Institute for Mental Health, which partially funded the study, adds, "These new results recommend a fresh look at our diagnostic categories. If some of the same genetic risks underlie schizophrenia and bipolar disorder, perhaps these disorders originate from some common vulnerability in brain development."

Professor Ian Hickie – executive director of consortium member the Brain and Mind Research Institute, University of Sydney, Australia – says, "This is a key study from both a conceptual and a practical perspective. It provides striking evidence for the common genetic risk factors for the major psychiatric disorders. The race will now focus on identification of the key neurodevelopmental genes that underpin these disabling conditions."

The study was supported by grants from the Stanley Medical Research Foundation through the Stanley Center for Psychiatric Research, and the Sylvan Herman Foundation. Other major funding bodies include the U.K. Medical Research Council, Wellcome Trust, and the Science Foundation Ireland.


Story Source:

The above story is based on materials provided by Massachusetts General Hospital. Note: Materials may be edited for content and length.


Journal Reference:

  1. Purcell SM, et al. Common polygenic variation contributes to risk of schizophrenia that overlaps with bipolar disorder. Nature, July 1, 2009 DOI: 10.1038/nature08185

Cite This Page:

Massachusetts General Hospital. "Many Genetic Contributions To Schizophrenia, Bipolar Disorder Discovered." ScienceDaily. ScienceDaily, 2 July 2009. <www.sciencedaily.com/releases/2009/07/090701131303.htm>.
Massachusetts General Hospital. (2009, July 2). Many Genetic Contributions To Schizophrenia, Bipolar Disorder Discovered. ScienceDaily. Retrieved July 30, 2014 from www.sciencedaily.com/releases/2009/07/090701131303.htm
Massachusetts General Hospital. "Many Genetic Contributions To Schizophrenia, Bipolar Disorder Discovered." ScienceDaily. www.sciencedaily.com/releases/2009/07/090701131303.htm (accessed July 30, 2014).

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