Researchers identify genetic mutations that may cause schizophrenia
Schizophrenia affects around 2.4 million adults in the US. The exact cause of the condition is unknown, but past research has suggested that genetics may play a part. Now, investigators from the Columbia University Medical Center in New York, NY, have uncovered clues that may build on this concept.
The research team, including Dr. Joseph Gogos, professor of biology, physiology and cellular biophysics at Columbia University Medical Center (CUMC), recently published their findings in the journal Neuron.
Schizophrenia is a disabling brain disorder that can cause a person to experience delusions, hallucinations, abnormal thought processes and even agitated body movements. Onset of the condition is most common between the ages of 16 and 30.
Although the cause of schizophrenia is unknown, researchers have established that the condition is hereditary. Around 1% of the general population have the illness, but it occurs in around 10% of individuals who have a first-degree relative with the condition, such as a parent, brother or sister.
According to the CUMC research team, past studies have focused on searching for individual genes that may contribute to the development of schizophrenia. But they note that new high-throughput DNA sequencing technology is now available, which allows researchers to investigate whether a combination of genes may trigger schizophrenia.
SETD1A gene may play a significant role in development of schizophrenia
For their study, the team used the new DNA sequencing technology to analyze the genomes of 231 patients with schizophrenia and their parents, who did not have the condition.
They focused specifically on the "exome" of the human genome - a region responsible for coding proteins.
Researchers used new high-throughput DNA sequencing technology to discover loss-of-function mutations in the SETD1A gene, which may contribute to schizophrenia.
Image credit: Dr. Joseph Gogos and Dr. Maria Karayiorgou.
On comparing sequencing data between schizophrenic patients and their parents, the researchers discovered an excess of loss-of-function mutations - rare mutations that pose severe damage to ordinary gene function - present in a variety of genes across different chromosomes. These mutations were found in schizophrenic patients but not their parents.
The team then found that many of the gene mutations passed down from parents to schizophrenia patients are loss-of function types. In addition, the team found that in genes that had a "low tolerance" for genetic variation, loss-of-function mutations were more common.
Further investigation into the sequencing data revealed that two of the loss-of-function mutations occurred in a gene called SETD1A. The team says this indicates that the SETD1A gene plays a significant role in the development of schizophrenia.
The SETD1A gene plays a part in chromatin modification - an important cellular process that reduces the size of DNA so it can fit inside a cell and regulate gene expression.
There is mounting research suggesting that damage to genes involved in chromatin modification, such as SETD1A, commonly occurs in psychiatric and neurodevelopment disorders, the researchers say.
Discovery could lead to early detection and treatment for schizophrenia
Co-author Dr. Maria Karayiorgou, professor of psychiatry at CUMC, says these findings help "define a specific genetic mechanism" that in part explains the heritability and development of schizophrenia.
"Accumulation of damaged genes inherited from healthy parents leads to higher risk not only to develop schizophrenia, but also to develop more severe forms of the disease," she adds.
Dr. Gogos says the team's findings may lead to new strategies for early detection and treatment for schizophrenia:
"A clinical implication of this finding is the possibility of using the number and severity of mutations involved in chromatin regulation as a way to identify children at risk of developing schizophrenia and other neurodevelopmental disorders.
Exploring ways to reverse alterations in chromatic modification and restore gene expression may be an effective path toward treatment."
The team says they plan to conduct further DNA sequencing studies in order to discover more genes that may contribute to the development of schizophrenia.
Earlier this year, Medical News Today reported on a study led by researchers from Cardiff University in the UK, which also detailed the discovery of genetic mutations that may cause schizophrenia.
Written by Honor Whiteman
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