A team of over 250 researchers from more than 20 countries have discovered that common genetic variations contribute to a person's risk of schizophrenia and bipolar disorder.
The study of more than 50,000 adults ages 18 and older provides new molecular evidence that 11 DNA regions in the human genome have strong association with these diseases, including six regions not previously observed. The researchers also found that many of these DNA variants contribute to both diseases.
The findings, reported by the Psychiatric Genome-Wide Association Study Consortium and published online in two papers in the journal Nature Genetics, represent significant advances in the understanding the causes of these chronic, severe, and debilitating disorders.
Also known as a whole genome association study, a genome-wide association study examines all or most of the genes of different individuals to see how much the genes vary from individual to individual.
"This is the largest study of its kind by far," said Patrick F. Sullivan, MD, Ray M. Hayworth & Family Distinguished Professor of Psychiatry and professor of genetics at the University of North Carolina at Chapel Hill. Sullivan, a PGC coordinator and principal investigator in the study, is also a member of the UNC Lineberger Comprehensive Cancer Center and the Carolina Center for Genome Sciences.
The study that focused on schizophrenia identified "strong evidence for seven different places in the human genome, five of which were new and two previously implicated, that contain DNA changes that are significantly associated with schizophrenia," Sullivan said.
And in a joint analysis of a schizophrenia and bipolar disorder sample, the Consortium found three different DNA regions, or loci, in which both disorders reached genome-wide statistical significance. "This tells us that these disorders, which many of us have considered to be separate things, actually share fundamental similarity," Sullivan said.
Schizophrenia and bipolar disorder are common and often devastating brain disorders. 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 affect about 1 percent of the world's population and usually strike in late adolescence or early adulthood.
Despite the availability of treatments, these illnesses are usually chronic, and response to treatment 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 consortium is the largest research consortium ever in psychiatry and is certainly the largest biological experiment we've ever done in the field," Sullivan said.
"We are studying on the order of 90,000 individuals across multiple disorders, while trying to do something for the greater good, which is effectively to go as far and as deep as we can in understanding the genomics of mental illness."
The research was funded by numerous European, U.S., and Australian funding bodies. Funds for coordination of the consortium were provided by the National Institute of Mental Health in Bethesda, Md.
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