Nav: Home

Researchers find high-risk genes for schizophrenia

April 22, 2019

Using a unique computational "framework" they developed, a team of scientist cyber-sleuths in the Vanderbilt University Department of Molecular Physiology and Biophysics and the Vanderbilt Genetics Institute (VGI) has identified 104 high-risk genes for schizophrenia.

Their discovery, which was reported in the journal Nature Neuroscience, supports the view that schizophrenia is a developmental disease, one which potentially can be detected and treated even before the onset of symptoms.

"This framework opens the door for several (research) directions," said the paper's 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.

Ultimately, 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."

Schizophrenia is a chronic, severe mental disorder characterized by hallucinations and delusions, "flat" emotional expression and cognitive difficulties. Symptoms usually 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 percent of the population, the risk rises sharply to 50 percent 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.

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.

Which genes have high rates of mutation? Which are expressed in prenatally? These are the kind of questions a genetic "detective" might ask to identify and narrow the list of "suspects."

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. But, said Chen, "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.
-end-
Also contributing to the study were Li's lab members Qiang Wei, PhD, Ying Ji, Hai Yang, PhD, VGI investigators Xue Zhong, PhD, Ran Tao, PhD, and James Sutcliffe, PhD, and VGI Director Nancy Cox, PhD. Special thanks go to investigators in the Vanderbilt Center for Neuroscience Drug Discovery -- Colleen Niswender, PhD, Branden Stansley, PhD, and center Director P. Jeffrey Conn, PhD -- for their critical input.

The study was supported by the Vanderbilt Analysis Center for the Genome Sequencing Program and National Institutes of Health grant HG009086.

Vanderbilt University Medical Center

Related Autism Articles:

Brain protein mutation from child with autism causes autism-like behavioral change in mice
A de novo gene mutation that encodes a brain protein in a child with autism has been placed into the brains of mice.
Autism and theory of mind
Theory of mind, or the ability to represent other people's minds as distinct from one's own, can be difficult for people with autism.
Potential biomarker for autism
A study of young children with autism spectrum disorder published in JNeurosci reveals altered brain waves compared to typically developing children during a motor control task.
Autism and the smell of fear
Autism typically involves the inability to read social cues. We most often associate this with visual difficulty in interpreting facial expression, but new research at the Weizmann Institute of Science suggests that the sense of smell may also play a central role in autism.
Autism often associated with multiple new mutations
Most autism cases are in families with no previous history of the disorder.
More Autism News and Autism Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Rethinking Anger
Anger is universal and complex: it can be quiet, festering, justified, vengeful, and destructive. This hour, TED speakers explore the many sides of anger, why we need it, and who's allowed to feel it. Guests include psychologists Ryan Martin and Russell Kolts, writer Soraya Chemaly, former talk radio host Lisa Fritsch, and business professor Dan Moshavi.
Now Playing: Science for the People

#537 Science Journalism, Hold the Hype
Everyone's seen a piece of science getting over-exaggerated in the media. Most people would be quick to blame journalists and big media for getting in wrong. In many cases, you'd be right. But there's other sources of hype in science journalism. and one of them can be found in the humble, and little-known press release. We're talking with Chris Chambers about doing science about science journalism, and where the hype creeps in. Related links: The association between exaggeration in health related science news and academic press releases: retrospective observational study Claims of causality in health news: a randomised trial This...