Researchers Contribute to New Findings on the Genetics of Schizophrenia and Bipolar Disorder

Posted on: 03 July 2009

New evidence suggests that many common DNA variants contribute to a person’s risk of schizophrenia, a common mental disorder affecting about one in a hundred of the adult Irish population. Surprisingly, many of the same DNA variants also appear to be involved in bipolar disorder. The findings, reported by the International Schizophrenia Consortium are published online this month in the journal Nature.

“The study found evidence that many DNA variants, commonly occurring in the population, combine to increase the risk that an individual develops  the disorder. These findings were  unexpected and provide a new perspective on the genetics of these diseases. Our challenge now is to  understand how these findings map  biological pathways in the brain and contribute to  schizophrenia and bipolar disorder,” says Dr Aiden Corvin, Head of the Psychosis Research Group at Trinity College Dublin and a co-author of the paper.

Schizophrenia is a brain disorder characterised by persistent delusions and hallucinations. Treatments are available, but response is variable in many cases and the underlying biology remains elusive. It has long been known that genetic inheritance and environmental risk factors contribute to disease risk, but it was assumed that only a small number of genes would be implicated. With the purpose of understanding the genetic mechanisms involved, senior researchers from 11 institutes in Europe and the US came together in 2006 to form the International Schizophrenia Consortium. In 2008, the group reported an excess of rare structural variation in the genomes of people with schizophrenia, suggesting that very rare deletions or duplications of small parts of the genome may contribute to risk for some individuals.

The current study, exploiting technological advances, tested hundreds of thousands of DNA variants (single nucleotide polymorphisms) in more than 3,300 individuals with schizophrenia and 3,600 individuals without the disorder. The study identified a contribution to susceptibility from genes known to be involved in immunity and in the regulation of  expression of other genes.  Most significantly the study showed that the same large number of DNA variants was more common in all groups of schizophrenia patients even though they were collected in different countries. These schizophrenia-related DNA variants were also more likely to exist in individuals with bipolar disorder. This finding is particularly striking, as these two disorders are often thought of as distinct, although related. The work was funded by grants from the Stanley Medical Research Foundation, and other funders including Science Foundation Ireland.

“How these genetic variants translate into schizophrenia or bipolar disorder for a given patient is not yet known. So they cannot currently be used as a diagnostic test or to predict an individual’s personal risk,” stressed co-authors Shaun Purcell, PhD and Pamela Sklar, MD, PhD from the Massachusetts General Hospital, Department of Psychiatry.

Taken together, the two International Schizophrenia Consortium studies provide new insights into the involvement of common and rare DNA variation in schizophrenia and into its complex relationship with bipolar disorder.

Notes to Editor:
The Trinity College Dublin Psychosis Research Group (Principal Investigators, Dr Derek Morris, Dr Gary Donohoe and Dr Aiden Corvin) is part of the Neuropsychiatric Genetics Research Group (NRG), headed by Professor Michael Gill ( at the university. Work at the NGRL in schizophrenia, bipolar disorder, autism and attention deficit hyperactivity disorder (ADHD)  funded by Science Foundation Ireland, the Health Research Board, the Wellcome Trust, Autism Speaks, and others is focusing on identifying and characterizing the biological processes that contribute to psychiatric diseases.

Institutional Members of the International Schizophrenia Consortium
Department of Psychiatry and Institute of Molecular Medicine, Trinity College Dublin, Ireland
Institute of Medical Sciences, University of Aberdeen, Aberdeen, Scotland
MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Cardiff, Wales
School of Molecular and Clinical Medicine, University of Edinburgh, Edinburgh, Scotland
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
Department of Psychiatry, Center for Human Genetic Research, Massachusetts General Hospital,
Departments of Genetics, Psychiatry, and Epidemiology, University of North Carolina at Chapel Hill
Queensland Institute of Medical Research, Queensland, Australia
Center for Genomic Psychiatry, University of Southern California, Los Angeles
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Mass.
Department of Mental Health Sciences, University College London Medical School, Windeyer Institute of Medical Sciences, London, England