Genes underscore five psychiatric disorders

Summary: Nineteen gene sets have been identified that contribute to at least five psychiatric disorders. The gene sets were associated with ADHD, ASD, bipolar disorder, major depressive disorder, and schizophrenia.

Source: University of Queensland

A group of international doctors has uncovered the genes that contribute to the development of ADHD, autism spectrum disorder, bipolar disorder, major depression and schizophrenia.

A collaborative research project carried out by The University of Queensland and Vrije Universiteit in Amsterdam analyzed more than 400,000 individuals to determine the genes behind these five psychiatric disorders.

UQ psychiatrist Professor Christel Middeldorp said several sets of genes marked all five disorders.

“Before this analysis, we knew a lot of psychiatric disorders were related to each other due to their hereditary nature,” Professor Middeldorp said.

“We often see multiple family members with mental illness in one family, but not necessarily with the same disorder.”

“We investigated if specific sets of genes were involved in the development of multiple disorders, which genes are not only related to say, ADHD, but also to the other four psychiatric disorders.”

“These are genes that play a role in the same biological pathway or are active in the same tissue type.”

“Genes that are highly expressed in the brain were shown to affect the different disorders, and some genes were related to all the illnesses we studied.”

“It shows that there is a common set of genes that increase your risk for all five disorders.”

The study’s lead author Dr Anke Hammerschlag said it was due to the biological pathways shared by the genes in the brain.

This shows a dna puzzle

New pharmaceutical drugs could potentially target these shared pathways. The image is adapted from the University of Queensland news release.

“We found that there are shared biological mechanisms acting across disorders that all point to functions in brain cells,” Dr Hammerschlag said.

“The synapse plays a vital role as this is the connection point between brain cells where the cells communicate with each other.”

“We also found that genes especially active in the brain are important, while genes active in other tissues do not play a role.”

New pharmaceutical drugs could potentially target these shared pathways.

“Our findings are an important first step towards the development of new drugs which may be effective for a wide range of patients, regardless of their exact diagnosis,” she said.

“This knowledge will bring us closer to the development of more effective personalized medicine.”

About this neuroscience research article

Source:
University of Queensland
Media Contacts:
Christel Middeldorp – University of Queensland
Image Source:
The image is adapted from the University of Queensland news release.

Original Research: Open access
“Synaptic and brain-expressed gene sets relate to the shared genetic risk across five psychiatric disorders”. Christel Middeldorp et al.
Psychological Medicine. doi:10.1017/S0033291719001776

Abstract

Synaptic and brain-expressed gene sets relate to the shared genetic risk across five psychiatric disorders

Background
Mounting evidence shows genetic overlap between multiple psychiatric disorders. However, the biological underpinnings of shared risk for psychiatric disorders are not yet fully uncovered. The identification of underlying biological mechanisms is crucial for the progress in the treatment of these disorders.

Methods
We applied gene-set analysis including 7372 gene sets, and 53 tissue-type specific gene-expression profiles to identify sets of genes that are involved in the etiology of multiple psychiatric disorders. We included genome-wide meta-association data of the five psychiatric disorders schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorder, and attention-deficit/hyperactivity disorder. The total dataset contained 159 219 cases and 262 481 controls.

Results

We identified 19 gene sets that were significantly associated with the five psychiatric disorders combined, of which we excluded five sets because their associations were likely driven by schizophrenia only. Conditional analyses showed independent effects of several gene sets that in particular relate to the synapse. In addition, we found independent effects of gene expression levels in the cerebellum and frontal cortex.

Conclusions
We obtained novel evidence for shared biological mechanisms that act across psychiatric disorders and we showed that several gene sets that have been related to individual disorders play a role in a broader range of psychiatric disorders.

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