UNC researchers part of study on schizophrenia underpinnings
Researchers from the University of North Carolina School of Medicine were part of a multinational study that identified more than 100 locations on the human genome associated with risk for developing schizophrenia.
The effort is the largest genomic study on any psychiatric disorder to-date, according to a news release from UNC Health Care, and may lead to new treatment approaches for the disorder. The findings were published online Tuesday in the journal Nature.
“The paper is a landmark,” said Dr. Patrick Sullivan, a study co-author, a distinguished professor of genetics and psychiatry at UNC and director of the Center for Psychiatric Genomics, in a prepared statement. “We have never before had such a profound and important look into the inner workings of schizophrenia.”
Schizophrenia is debilitating psychiatric disorder that affects about 1 out of every 100 people in the world. It’s characterized by hallucinations, paranoia, and a breakdown of thought processes, and often emerges in the teens and early 20s.
Despite the need for treatment, medications on the market treat only one of the disorder symptoms– psychosis -- and do not address the debilitating cognitive symptoms of schizophrenia.
In part, treatment options are limited because the biological mechanisms underlying schizophrenia have not been understood. No medications with fundamentally new mechanisms of action have been developed since the 1950s.
In the genomics era, research has focused on the genetic underpinnings of schizophrenia because of the disorder’s high heritability. Roughly two dozen genomic regions have been found to be associated with the disorder.
The new study confirms those earlier findings, and builds on them. The authors looked at more than 80,000 genetic samples from schizophrenia patients and healthy volunteers and found 108 specific locations in the human genome associated with risk for the disorder. Eighty-three of those loci had not previously been linked to the disorder.
“In just a few short years, by analyzing tens of thousands of samples, our consortium has moved from identifying only a handful of loci associated with schizophrenia, to finding so many that we can see patterns among them,” said first author Stephan Ripke, a scientist at the Broad Institute’s Stanley Center for Psychiatric Research and the Translational Genetics Unit at Massachusetts General Hospital, in a statement. “We can group them into identifiable pathways – which genes are known to work together to perform specific functions in the brain.”
Among other findings, the study implicates genes expressed in brain tissue; particularly those related to neuronal and synaptic function. These include genes that are active in pathways controlling synaptic plasticity – a function essential to learning and memory – and pathways governing postsynaptic activity, such as voltage-gated calcium channels, which are involved in signaling between cells in the brain.
Additionally, the researchers found a smaller number of genes associated with schizophrenia that are active in the immune system.
And it found an association between the disorder and the region of the genome that holds the gene that produces the dopamine receptor targeted by all approved medications for schizophrenia. That suggests that other loci uncovered in the study may point to additional therapeutic targets.
The study is the result of years of work by the Schizophrenia Working Group of the Psychiatric Genetics Consortium, an international, multi-institutional collaboration founded in 2007 to do large analyses of genetic data for psychiatric disease.