In the largest genome study ever conducted on any psychiatric disorder, an international team of researchers identified more than 100 genes linked to the development of schizophrenia. The findings, published online in the journal Nature, could lead to new approaches to treating the disease, which has seen little improvement in drug development in more than 60 years.
Current schizophrenia drugs treat only one of the symptoms of the disorder (psychosis), and do not help ease the devastating cognitive symptoms. In part, treatment options are limited because the biological mechanisms underlying the illness are not well understood.
Research on schizophrenia has focused on genes because of the disorder’s high heritability. Previous studies have shown the complexity of the disease (it is potentially caused by the combined effects of many genes), and roughly two dozen genomic regions have been linked to the disorder. The new study confirms those earlier findings and sheds even more light on the genetic basis of schizophrenia and its underlying biology.
“By studying the genome, we are getting a better handle on the genetic variations that are making people vulnerable to psychiatric disease,” said National Institute of Mental Health Director Thomas Insel.
“Through the wonders of genomic technology, we are in a period in which, for the first time, we are beginning to understand many of the players at the molecular and cellular level.”
In the genome-wide association study (GWAS), the researchers analyzed 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 schizophrenia. Eighty-three of those loci (specific locations of genes) had not been linked previously 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’s Stanley Center for Psychiatric Research.
“We can group them into identifiable pathways — which genes are known to work together to perform specific functions in the brain. This is helping us to understand the biology of schizophrenia.”
For the most part, the study points to genes expressed in brain tissue. The researchers also found a smaller number of schizophrenia genes that are active in the immune system — a finding that offers support for a previously hypothesized link between schizophrenia and immunological processes.
The study also found a link between schizophrenia and the region of the genome that holds the gene known as DRD2. This gene produces the dopamine receptor targeted by all approved medications for schizophrenia. This finding suggests that the new gene locations may also become therapeutic targets.
“The fact that we were able to detect genetic risk factors on this massive scale shows that schizophrenia can be tackled by the same approaches that have already transformed our understanding of other diseases,” said the paper’s senior author, Michael O’Donovan, deputy director of the MRC Centre for Neuropsychiatric Genetics and Genomics at Cardiff University School of Medicine. ‘
The wealth of new findings have the potential to kick-start the development of new treatments in schizophrenia, a process which has stalled for the last 60 years.”
Source: Harvard University