ADHD, disruptive behaviour and aggression are genetically correlated

Therapy Breakthroughs 18. okt 2021 2 min Professor Ditte Demontis Written by Kristian Sjøgren

People with both attention-deficit/hyperactivity disorder (ADHD) and disruptive behaviour disorders appear to have increased load in their genomes of the genetic variants involved in aggressive behaviour.

A new study has mapped the genetics underlying comorbid ADHD and disruptive behaviour disorders. The research shows that genetic variants at three locations in the genome appear to predispose to being diagnosed with both disorders.

The research also reveals that people with ADHD plus disruptive behaviour disorders have more genetic variants that are involved in aggression among the children without the disorders.

A researcher behind the study says that the results may help to destigmatise having disruptive behaviour disorders.

“Our research suggests that the aggressive behaviour of people with disruptive behaviour disorders is largely caused by the same genetic architecture associated with aggressive behaviour among children without disruptive behaviour disorders. People with disruptive behaviour disorders have increased load of the genetic variants associated with aggressive behaviour in their genome. This discovery can perhaps be used to better understand their aggressive behaviour, since this seems, at least to some extent, to be caused by the same biological mechanisms as aggressive behaviour in general,” explains Ditte Demontis, Associate Professor, Department of Biomedicine, Aarhus University.

The research has been published in Nature Communications.

Disruptive behaviour disorders are serious

Although many are probably not familiar with disruptive behaviour disorders, they are very serious. Examples include oppositional defiant disorder and conduct disorder.

Children with disruptive behaviour disorders externalise, and tend to exhibit aggressive behaviour and reduced empathy. For example, they may continue to hit other children, even after these children end up on the floor, and they also bully other children and mistreat animals. Having these disorders increases the risk of having antisocial personality disorder as an adult.

Ditte Demontis and colleagues investigated the genetic background of people with both ADHD and disruptive behaviour disorders.

“Some childhood mental disorders often occur together in the same individual, and about 2% of all children have both ADHD and disruptive behaviour disorders. We mapped the underlying genetic component, which makes good sense, since improving insight into the biology behind these disorders can potentially help many children in the long term,” says Ditte Demontis.

Three sites in the genome predispose to ADHD plus disruptive behaviour disorders

Ditte Demontis and colleagues analysed genetic data from 3,800 people with both ADHD and disruptive behaviour disorders and genetic data from 31,300 controls.

The researchers then performed a genome-wide meta-analysis to identify genetic variants associated with increased risk of having the two comorbid disorders. The researchers investigated whether the people with the disorders had specific genetic variants more often than the controls, which would indicate a genetic association.

Data were obtained from seven cohorts: the renowned nationwide iPSYCH cohort from Denmark and six other European cohorts.

The study identified three genome-wide significant loci associated with increased risk of ADHD plus disruptive behaviour disorders.

The researchers also analysed genetic data from a cohort from China and confirmed that a genetic variant in chromosome 11 appears to predispose to having ADHD plus disruptive behaviour disorders across European and Chinese ancestries.

“Having this genetic variant does not necessarily mean that a child develops ADHD plus disruptive behaviour disorders. The risk only increases slightly, and it is the combined effect of many genetic variants as well as the environment that lead to a higher risk of developing ADHD plus disruptive behaviour disorders. Although we have only identified the tip of the iceberg in this study, we can use the results to improve insight into the biological signalling pathways that may be involved in these disorders and eventually to find new drugs to treat them,” explains Ditte Demontis.

Aggressive behaviour and behavioural disorders closely associated

The researchers also examined the polygenic architecture, which is like examining the genome from a helicopter perspective.

In this part of the study, the researchers compared their results with those of previous studies of the genetic background of aggressive behaviour among children without ADHD and disruptive behaviour disorders.

The polygenic architecture between the two data sets was highly correlated at r = 0.81 (1.00 is a perfect correlation).

“We found considerable overlap between the genetics that influences aggressive behaviour and the genetics that underlies ADHD plus disruptive behaviour disorders, meaning that many of the variants involved in aggression are also involved in ADHD plus disruptive behaviour disorders,” concludes Ditte Demontis.

Our research focuses on identification of genetic risk factors for externalizing childhood psychiatric disorders including ADHD and conduct disorder a...

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