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Queensland researchers help explain genetic makeup of schizophrenia and bipolar disorder

Published by: Andrew Taylor

Researchers at the Queensland Institute of Medical Research (QIMR) are helping scientists understand the genetic makeup of schizophrenia and bipolar disorder.

By using novel analytical techniques developed by QIMR’s Dr Naomi Wray and Professor Peter Visscher, researchers have discovered that many common genetic variants contribute to a person’s risk of schizophrenia and these variants can explain at least a third of the risk of inheriting the disease.

According to QIMR’s Dr Wray, this work provides the first molecular evidence that this form of genetic variation is involved in schizophrenia. Even though the DNA samples were collected by different investigators and tested in different laboratories around the world, the same large group of genetic variants was found to be common in all groups of schizophrenia patients.

The research also found that the schizophrenia-related variants are common in people with bipolar disorder but not in people with non-psychiatric diseases. This is highly significant as schizophrenia and bipolar disorder are considered to be distinct, although related, conditions.

“Crucial to the success of the project was the willingness of researchers to share thousands of patient DNA samples collected over many years. Hundreds of thousands of genetic variants were tested in more than 3,300 individuals with schizophrenia and 3,600 individuals without the disorder”, said Dr Wray.

“Our new technique allowed the simultaneous consideration of thousands of genetic variants at a time. Compared to standard methods which look at single variants, this provides much richer information, accumulating the small effects of individual variants“, explained Professor Visscher.The findings 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.

According to Professor Michael Breakspear, Head of QIMR’s newly formed Division of Mental Health, “This landmark study provides strong evidence for an important but previously unverified theory of schizophrenia – namely that much of the genetic risk comes from the combined effect of many – literally thousands – of genetic variations.”

“The study also reveals striking evidence for common genetic risk factors for the two major psychotic disorders – schizophrenia and bipolar disorder. This work will ultimately help improve the diagnostic and therapeutic options for patients and their families”, said Professor Breakspear.

Schizophrenia is a common and often devastating brain disorder characterized by persistent delusions and hallucinations.  It affects about one in every 100 people throughout the world 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.

The findings are reported by the International Schizophrenia Consortium, of which QIMR is an active member, and published online in the journal Nature.

Formed in 2006, the International Schizophrenia Consortium brings together senior researchers from 11 institutes around the world. It is led by Drs Pamela Sklar and Shaun Purcell of the Broad Institute of MIT and Harvard. Major funding and resources for the current work were provided by the Broad Institute’s Stanley Center for Psychiatric Research, Cambridge. Drs Wray and Visscher receive funding from the Australian National Health and Medical Research Council to apply their methods to the data generated by the consortium.