Scientists identify new genes responsible for four serious mental illnesses

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Researchers have identified 70 previously unknown genes that contribute to people developing the serious mental health disorders schizophrenia, bipolar disorder, depression and Attention Deficit Hyperactivity Disorder (ADHD).

The findings have been published today in the prestigious journal Nature Genetics. The study was led by the head of QIMR Berghofer’s Translational Neurogenomics Group, Professor Eske Derks, in collaboration with scientists from Vanderbilt University and the University of Amsterdam. 

Professor Derks said her team also identified how the activity, or expression, of those 70 new genes, and 261 other genes that were already linked to mental illnesses, increased the disease risk.

There is a growing body of evidence that genetic risk factors and environmental triggers such as stress and trauma can cause schizophrenia, bipolar disorder, depression and ADHD.

“In this study we are homing in on the biological causes of these mental illnesses,” Professor Derks said.

The researchers examined data from tens of thousands of people collected from four separate studies into schizophrenia, bipolar disorder, depression and ADHD and compared it to information from hundreds of thousands of healthy controls who were classified as not having mental illnesses.

“For schizophrenia for example we looked at the genetic data from about 40,000 patients and compared it to data from about 65,000 control samples from people without the disorder,” she said.

“Through this process we identified 275 genes whose activity levels contribute to the risk of schizophrenia, 13 genes whose expression is associated with bipolar disorder, 31 genes involved in depression and 12 for ADHD. We can now conduct follow up tests of those particular genes.”

The study also looked at the DNA and gene activity, or expression, in brain, colon, adrenal gland and whole blood tissue samples from 700 deceased donors who had not been diagnosed with psychiatric disorders during their lives, to gain an understanding of where in the body the gene activity was taking place.

“This extra level of inquiry proved very valuable because 137 of the 331 genes (41 per cent) were found solely in brain tissue while only 24 per cent of the genes were detected in the easily accessible blood tissue,” Professor Derks said.

“This study narrows the field on which genes contribute to these four serious mental disorders.

“Recent studies have found associations between the disorders and large regions of the genome, but they didn’t reveal which particular genes were responsible or how the genes’ activity affected the risk of developing a mental illness.

“We pinpointed a smaller set of genes and looked at how much their level of expression in different tissues such as brain, colon, adrenal gland, and blood, contributed to symptoms.

“This study provides more evidence about the genetic basis of these diseases and by better understanding the biology of the genes, attention can turn to finding the best drugs or treatments to manage them.

“It’s not enough that we know that gene X is involved in a disease, we need to know exactly what it is doing. Is it too active or not active enough and how do we change its level of activity to prevent or even
stop symptoms?

“We’ll now be working on exploring drug repurposing – to see if any existing drugs that have already been approved for human use can act on any of these genes or combination of genes.

“Also, importantly, this study has again confirmed that genetics, along with environmental risk factors, influence the possibility of developing these mental health disorders and adds weight to the need for
more genetic research to better understand why some people are more vulnerable to developing mental illness.”

Professor Derks said she hoped to use the same approach of integrating genetic and gene expression data in the future to understand which genes are responsible for other psychiatric disorders such as obsessive compulsive disorder, substance abuse, anorexia and other eating disorders.

 
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