Researchers have uncovered 104 high-risk genes for schizophrenia

Researchers have uncovered 104 high-risk genes for schizophrenia
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Scientists have identified high-risk genes for schizophrenia, suggesting it to be a developmental disease that can be detected & treated before the onset of symptoms.

Reported in the journal Nature Neuroscience, using a unique computational framework they developed, a team of scientists in the Vanderbilt University Department of Molecular Physiology and Biophysics and the Vanderbilt Genetics Institute (VGI) have identified 104 high-risk genes for schizophrenia. Their discovery supports the view that schizophrenia is a developmental disease, one which potentially can be detected and treated even before the onset of symptoms.

Creating a targeted drug for schizophrenia

“This framework opens the door for several (research) directions,” explains senior author, Bingshan Li, PhD, associate professor of Molecular Physiology and Biophysics and an investigator in the Vanderbilt Genetics Institute (VGI).

One direction is to determine whether drugs already approved for other, unrelated diseases could be “repurposed” to improve the treatment of schizophrenia. Another is to find in which cell types in the brain these genes are active along the development trajectory, could this research reduce the negative impact of schizophrenia.

Li said, “I think we’ll have a better understanding of how prenatally these genes predispose risk and that will give us a hint of how to potentially develop intervention strategies. It’s an ambitious goal … (but) by understanding the mechanism, drug development could be more targeted.”

High-risk genes and schizophrenia

Schizophrenia is a chronic, severe mental disorder characterised by hallucinations, delusions and cognitive difficulties. Symptoms can start between the ages of 16 and 30. Antipsychotic medications can relieve symptoms but there is no cure for the disease.

Genetics plays a major role. While schizophrenia occurs in 1% of the population, the risk rises sharply to 50% for a person whose identical twin has the disease.

Recent genome-wide association studies (GWAS) have identified more than 100 loci, or fixed positions on different chromosomes, associated with schizophrenia. That may not be where high-risk genes are located, however. The loci could be regulating the activity of the genes at a distance, nearby or very far away.

Identifying high-risk genes

To solve the problem Li, with first authors Rui Chen, PhD, research instructor in Molecular Physiology and Biophysics, and postdoctoral research fellow Quan Wang, PhD, developed a computational “framework” they called the Integrative Risk Genes Selector.

The framework pulled the top genes from previously reported loci based on their cumulative supporting evidence from multi-dimensional genomics data, as well as gene networks.

The result was a list of 104 high-risk genes, some of which encode proteins targeted in other diseases by drugs already on the market. One gene is suspected in the development of autism spectrum disorder. “Schizophrenia and autism have shared genetics,” Chen said.

Much work remains to be done. Chen concludes: “Our framework can push GWAS a step forward … to further identify genes.” It also could be employed to help track down genetic suspects in other complex diseases.

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