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The Icahn School of Medicine at Mount Sinai has announced the publication of two papers in the journal Nature that reveal new information about the genetic complexity underpinning schizophrenia. These collaborative studies represent the largest exome sequencing efforts to date to elucidate this mental illness, and together found that the disorder is likely caused by far more rare genetic mutations than previously suspected.
In the publications, Mount Sinai scientists and their collaborators at the Broad Institute, Sanger Centre, Cardiff University, University of North Carolina, and the Karolinska Institute report large-scale projects that sequenced the genes of 6,948 people in Bulgaria and Sweden, including patients diagnosed with schizophrenia, their parents and healthy controls. Both studies determined that a very large number of rare genetic mutations contribute to risk for the disease, rather than only a few 'faulty' genes. The clinical and genetic information gathered on more than 3,000 affected individuals has produced the world's largest database on schizophrenia, a resource that will be invaluable to the biomedical community in continued efforts to elucidate factors that contribute to the disease.
"These new exome studies indicate that the genetic basis of schizophrenia is tremendously complex and will require further research to add RNA, protein, and other layers of data to the picture we are building," said Eric Schadt, PhD, the Jean C. and James W. Crystal Professor of Genomics at the Icahn School of Medicine at Mount Sinai, and Director of the Icahn Institute for Genomics and Multiscale Biology, part of the Mount Sinai Health System. "Now that we have this critical information, we can embark on the kind of massive-scale network analysis that our scientists have successfully used to characterize other complex diseases and start to think about new ways to treat these patients."
Schizophrenia is a chronic, often debilitating mental illness that affects 1 percent of the global population, including 2.4 million American adults. Symptoms include persistent auditory and visual hallucinations, delusions, and paranoia, among others. Patients today are treated with antipsychotic therapies that have seen little innovation in the last 20 years. Familial studies have consistently demonstrated a large role for inherited factors, arguing for continued genetic studies.
"The sheer volume of data generated in these projects is remarkable and suggests new ways of thinking about the role of rare mutations in schizophrenia," said Shaun Purcell, PhD, lead author of the Swedish population study and head of the Center for Statistical Genomics at Mount Sinai. "Although the complexity of the genetics is sobering, these types of studies should provide a firm base from which we can chart a course toward the ultimate goal of subtyping patients and offering a more personalized treatment path than the one-size-fits-all approach currently used."
Details of the two publications:
Funding for the studies was provided by the Friedman Brain Institute and the Icahn Institute for Genomics and Multiscale Biology at Mount Sinai, the National Institute of Mental Health, the National Human Genome Research Institute, the Sylvan Herman Foundation, a philanthropic gift from K. and E. Dauten, the Stanley Medical Research Institute, the Swedish Research Council, Medical Research Council, the European Community's Seventh Framework Programme, Fidelity Foundations, The Wellcome Trust, and the European Commission.
Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
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