Autism and attention-deficit/hyperactivity disorder associated with shared and disorder-specific genetic variants

Disease and treatment 29. nov 2022 3 min Professor Anders Børglum Written by Kristian Sjøgren

If a gene varies slightly in one way, this can lead to the development of attention-deficit/hyperactivity disorder (ADHD). Conversely, if the gene varies slightly in a different way, this can result in autism spectrum disorder (ASD). Research in Denmark shows that ADHD and ASD share many genetic traits but also differ. A researcher says that these differences can be used to improve diagnosis and develop medicines for the people with these disorders.

ADHD and ASD are separate developmental disorders but have many shared genetic traits. New research shows that they may result from the same genetic variants, which are important for brain development and function.

The research also shows that these disorders may also result from disorder-specific genetic variants, which can lead to either ADHD or ASD. These genetic variants are located in the same regions in the same genes, so even though some individuals may develop both ADHD and ASD, some genetic variants for ASD protect against ADHD and vice versa.

The results indicate how genetic screening could be used to investigate genes associated with higher risk for ADHD or ASD or both disorders and which genes can perhaps be targeted with medication in the future to curb the symptoms of ADHD and ASD.

“Now that we know about the genetic variants associated with the development of ADHD and ASD, we can also improve the investigation of how these variants affect the functions of the genes and thus learn more about what happens during brain development and later in life when people develop these mental and neurodevelopmental disorders. This will help us to better understand how to help people with ADHD and/or ASD,” explains a researcher behind the study, Anders Børglum, Professor, Department of Biomedicine, Aarhus University and iPSYCH, Denmark’s largest research project in psychiatry and genetics.

The research has been published in Nature Genetics.

Seven genetic variants associated with ADHD and ASD

The researchers examined genetic data for 34,462 people with ADHD or ASD and 41,201 healthy controls for the presence of 8.9 million genetic variants that have a frequency of more than 1% in the population.

These genetic variants are slight differences in genes, with one genetic component exchanged for another. This gives the underlying gene a slightly different function, which can affect the development or function of the brain and lead to neurodevelopmental disorders.

The researchers investigated differences in the presence of genetic variants between people with ADHD or ASD and the healthy controls.

In this part of the study, the researchers found that seven distinct loci appear more often in the genome of people with ADHD and ASD and are therefore probably linked to the development of the disorders.

One such gene is MANBA. Rare mutations in MANBA are associated with other types of nervous system disorders, including low intelligence, hearing loss and speech difficulty.

“These seven genetic variants influence the development of both ADHD and ASD, and we can use this knowledge to determine which biological processes in the brain are disrupted in both disorders,” says Anders Børglum.

ASD and ADHD associated with distinct genetic variants

However, the researchers went beyond finding shared genes for ADHD and ASD. In the second part of the study, they investigated whether any genetic variants are associated with the development of only ADHD or ASD.

They found that five genetic variants are associated with the development of only one disorder.

For each of the five genetic variants, an individual having one genetic component at this loci in the genome has an increased risk of developing ADHD, whereas an individual having another genetic component at the same loci in the genome has an increased risk of developing ASD.

The variants that increase the risk of developing ASD therefore appear to reduce the risk of developing ADHD and vice versa.

A review of the underlying genes shows that these are significant for brain development and function.

The researchers found that genetic variants in a gene affecting the function of histones are associated with an increased risk of developing either ADHD or ASD. The histones are large molecules around which DNA is wrapped, and previous research indicated that the histones play a role in developing ASD.

The researchers also identified that genetic variation in the CAMKV gene helps to promote either ADHD or ASD. CAMKV is important for the function of dendritic cells, which have also previously been associated with the development of ASD, low intelligence and delayed mental development.

“Further, we were very interested to find that some of the genetic variants identified affect cognitive function in the general population. We can specifically show that some of the gene variants associated with increased risk of developing ASD improve people’s cognitive function, whereas the complementary gene variants that increase the risk of developing ADHD are associated with impaired cognitive function,” explains Anders Børglum.

More rapid diagnosis

According to Anders Børglum, the findings on shared and disorder-specific genetic variants can be used to improve understanding of the biological processes in the brain related to developing ADHD and ASD.

This will also provide researchers with insight into how medication might be used to alleviate symptoms.

This could include developing drugs targeting the processes that are imbalanced in the development of ADHD or ASD.

Anders Børglum also says that the results can pave the way for improving the diagnosis of people with ADHD or ASD or both disorders.

People with both ADHD and ASD are often diagnosed with ASD first, and this may subsequently make diagnosing ADHD difficult, because the ASD diagnosis can be so overwhelming that it overshadows the ADHD symptoms.

Analysing genes associated with high risk of ADHD and ASD may enable researchers and doctors to more easily determine whether they should investigate more than ASD. Ultimately, this will give the parents of children with ADHD and/or ASD more rapid access to the right tools to make daily life function optimally.

“We always want to diagnose as early as possible so that we can give the families the tools they need as quickly as possible. Diagnosing either ADHD or ASD or both disorders makes a big difference,” concludes Anders Børglum.

In our group, we are engaged in identifying and characterising genes that play a role in mental disorders. Our overall goal is to gain more knowledge...

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