The mega-analysis, the largest to date for severe mental illness, identified 11 regions that are associated with these common, debilitating conditions. Six of the regions had not been previously identified. The researchers also found that many of these DNA variations contribute to both diseases. The findings, reported by the Psychiatric Genome-Wide Association Study Consortium (PGC) and published online in two papers in the journal Nature Genetics, represent significant advances in the understanding the causes of these chronic and life-changing disorders.
“This impressive world-wide collaborative effort has led us to new candidate genes for schizophrenia, which we are now following up with novel neurobiological studies in patients with schizophrenia,” said Anil Malhotra, MD, Director of Psychiatry Research at Zucker Hillside Hospital and an Investigator at the Feinstein Institute of Medical Research. “It is our hope that these findings will lead to a better understanding of the causes of the illness and, in the long run, provide the information needed to develop better treatments.” His research team participated in the schizophrenia study.
Schizophrenia and bipolar disorder are common, affecting one percent of the population (schizophrenia) and three percent (bipolar). Scientists have been searching for genetic explanations for years but many of the findings fail to be replicated by others in the field. In recent years, with more advanced technology, scientists have identified a number of promising leads.
Some of the most prominent symptoms in schizophrenia are persistent delusions, hallucinations and cognitive problems. Bipolar disorder (or manic-depressive illness) is characterized by episodes of severe mood problems including mania and depression. Both conditions usually strike in late adolescence or early adulthood. Despite the availability of treatments, the response to treatment is often incomplete. These conditions led 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.
One of the most interesting genetic findings in the mega-analysis is a genetic variant in the gene that codes for microRNA 137. MicroRNAs influence the expression of multiple proteins. The expression of this gene blocks the transcription of messenger RNA (mRNA). This single molecule works like a conductor of an orchestra who sends hands in one direction to silence many instruments at once. “It’s too soon to know what implications this could have for developing treatments,” Dr. Malhotra said.
Formed in 2007, the PGC is the largest consortium ever in psychiatry. Over 250 researchers from more than 20 countries have come together in an unparalleled spirit of cooperation to advance knowledge of the genetic causes of mental illness. Crucial to the success of the project was the willingness of many groups to share genetic data from tens of thousands of patients collected over many years. The research was funded by numerous European, US, and Australian funding bodies. Funds for coordination of the consortium were provided by the National Institute of Mental Health (NIMH) and a variety of public and private sponsors at the centers involved in the study.
Dr. Malhotra’s team received funding from the Donald and Barbara Zucker Family Foundation and the NIMH.
About The Feinstein Institute for Medical Research
Headquartered in Manhasset, NY, The Feinstein Institute for Medical Research is home to international scientific leaders in Parkinson’s disease, Alzheimer’s disease, psychiatric disorders, rheumatoid arthritis, lupus, sepsis, inflammatory bowel disease, diabetes, human genetics, leukemia, lymphoma, neuroimmunology, and medicinal chemistry. The Feinstein Institute, part of the North Shore-LIJ Health System, ranks in the top 6th percentile of all National Institutes of Health grants awarded to research centers. For more information: www.FeinsteinInstitute.org
Media Contact: Jamie Talan, science writer