A multinational group of investigators has discovered that people suffering from schizophrenia are far more likely to carry rare chromosomal structural changes of all types, particularly those that have the potential to alter gene function. In addition, the study uncovered two new specific genomic areas that, when altered, significantly increase the risk of developing the disease. The report from the International Schizophrenia Consortium, the largest and most complete such study to date, is being published online today by the journal Nature.
Schizophrenia is a common, chronic and often devastating brain disorder characterized by delusions and hallucinations. It affects approximately 1 person in 100 at some point in their lives and usually strikes in late adolescence or early adulthood. Despite the availability of effective treatments, the course of the illness is usually chronic, and response often limited, leading to prolonged disability and personal suffering. Family history, which signifies genetic inheritance, is the strongest risk factor for schizophrenia, but until now little has been known about the specific genes or chromosome regions involved.
“This surprising excess of many types of chromosomal changes in schizophrenia patients provides us with rich clues to follow up in future research,” says Pamela Sklar, MD, PhD, of the Department of Psychiatry and Center for Human Genetic Research at Massachusetts General Hospital (MGH), a Senior Associate Member of the Broad Institute of MIT and Harvard and corresponding author of the Nature paper. “This work opens up an entirely new way to think about schizophrenia and eventually will suggest new avenues for researching effective therapies for the sake of patients and families suffering from this terrible disorder.”
Formed in 2006, the International Schizophrenia Consortium is led by senior researchers from 11 institutes in Europe and the
The investigators used new genomic technologies and novel analytical techniques developed at the Broad Institute and at MGH to screen these samples for structural variants in the genome, sites where a portion of a chromosome is missing or duplicated. This unprecedented scale of cooperation allowed the analysis of enough data to identify schizophrenia-specific genome alterations – including the newly identified sites on chromosomes 1 and 15 and an area on chromosome 22 observed in earlier studies – as well as a subtle general increase in structural genomic variants in schizophrenia patients compared with controls. A second study also being published in Nature today confirms the association of those three genomic sites with increased risk for developing the disease.
“The Consortium should be recognized for taking the important first step towards unearthing the full underlying genomic architecture of schizophrenia and other psychotic disorders,” says Edward Scolnick, MD, Director of the
Thomas Insel, MD, director of the National Institute for Mental Health, which partially funded the study, adds,“By implicating two previously unknown sites, this study triples the number of genomic areas definitely linked to schizophrenia. It also confirms in a large sample that unraveling the secrets of rare structural genetic variation may hold promise for improved diagnosis, treatment and prevention of such neurodevelopmental disorders.”
Lead analyst Shaun Purcell, PhD, of the MGH Department of Psychiatry and Center for Human Genetic Research and an Associate Member of the Broad Institute at the Stanley Center, emphasizes that “the specific way a small overall increase in this kind of genetic variation translates into schizophrenia for a given patient is not yet known, especially given the common occurrence of these structural genomic variations in everyone.”
Professor Michael O’Donovan, FRCPsych, PhD, of
The study was supported by grants from the Stanley Medical Research Foundation through the
About the Broad
The Broad Institute of MIT and Harvard was founded in 2003 to bring the power of genomics to biomedicine. It pursues this mission by empowering creative scientists to construct new and robust tools for genomic medicine, to make them accessible to the global scientific community, and to apply them to the understanding and treatment of disease. The Institute is a research collaboration that involves faculty, professional staff and students from throughout the MIT and Harvard academic and medical communities. It is jointly governed by the two universities.