Researchers have created a test that is able to predict whether a person is at a higher or lower risk of schizophrenia.
Led by scientists at Indiana University, the research team identified a group of genes most associated with schizophrenia. Using a functional genomics approach that incorporates a number of experimental techniques, the scientists were able to apply the gene test to data from other schizophrenia studies and successfully identify which patients had been diagnosed with schizophrenia, according to the study, which was published online by the journal Molecular Psychiatry.
The prototype test was able to predict whether a person was at a higher or lower risk of schizophrenia in about two-thirds of cases, researchers report.
The researchers also propose that schizophrenia is a disease emerging from a mix of genetic variations affecting brain development and neuronal connections, along with environmental factors, particularly stress.
“At its core, schizophrenia is a disease of decreased cellular connectivity in the brain, precipitated by environmental stress during brain development, among those with genetic vulnerability,” said principal investigator Alexander B. Niculescu III, M.D., Ph.D., associate professor of psychiatry and medical neuroscience at the IU School of Medicine and director of the Laboratory of Neurophenomics at the IU Institute of Psychiatric Research. “For the first time we have a comprehensive list of the genes that have the best evidence for involvement in schizophrenia.”
When the test estimating the risk for schizophrenia is refined, it could provide guidance to caregivers and health care professionals about young people in families with a history of the disease, prompting early intervention and treatment, Niculescu said.
He emphasized that a score indicating a higher risk of schizophrenia “doesn’t determine your destiny. It just means that your neuronal connectivity is different, which could make you more creative, or more prone to illness. It’s all on a continuum — these genetic variants are present throughout the population. If you have too many of them, in the wrong combination, in an environment where you are exposed to stress, alcohol and drugs, and so on, that can lead to the development of the clinical illness.”
To identify and prioritize the genes involved in schizophrenia, the researchers combined data from several types of studies, including genome-wide association studies, gene expression data derived from human tissue samples, genetic linkage studies, genetic evidence from animal models, and other work. This approach, called convergent functional genomics, has been pioneered by Niculescu and colleagues, and relies on multiple independent lines of evidence to implicate genes in clinical disorders.
The researchers noted that the results were stronger when analyses were performed using gene-level data, rather than analyses based on individual mutations — called single nucleotide polymorphisms, or SNPs — in those genes. Multiple SNPs can spark a gene’s role in the development of schizophrenia, so evidence for the genes, and the biological mechanisms in which they play a role, was much stronger from study to study than evidence for individual SNPs.
“By better understanding the genetic and biological basis of the illness, we can develop better tests for it, as well as better treatments,” he said.