Your Genes Determine Whether You Get ADHD or Autism

There is a large overlap between the genetic causes of autism and ADHD. Now, researchers from Aarhus University have found gene variants that increase the risk of developing only one of the diagnoses and not the other.

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In the group of neurodevelopmental disorders, ADHD and autism have several things in common: They are two of the most common child psychiatric diagnoses, both diagnoses are highly heritable, and although they differ from each other in the core symptoms, autism and ADHD have a significant overlap in their underlying genetic causes.

Researchers have identified seven genetic variants common to autism and ADHD and five gene variants specific to only one of the two diagnoses.

"We have succeeded in identifying both shared genetic risk variants and genetic variants that differentiate the two developmental disorders," says Professor Anders Børglum of the Department of Biomedicine at Aarhus University and iPSYCH, Denmark's largest research project within psychiatry, which is behind the study.

"That means that we are beginning to understand both the biological processes that are behind the development of both diagnoses and - as something completely new - also the processes that push the developmental disorder specifically in the direction of either autism or ADHD."

What Happens in the Brain?

The genetic variants affect brain nerve cells and how the brain develops and communicates. It is also remarkable that some genetic variants impact people's cognitive functions.

Specifically, the researchers can, for example, see that some of the genetic variants that only increase the risk of autism also increase the cognitive functions of individuals, while the complementary variants, which only increase the risk of ADHD, generally reduce the cognitive functions of individuals.

Similarly, the researchers have identified a gene variant that increases the risk of autism and, simultaneously, reduces the volume of a specific brain area in people in the general population. In contrast, the complementary variant increases the risk of ADHD and increases the volume of this brain area.

Altered Diagnostic Guidelines

It may seem obvious, but the study is the first in the world to show that people with both ADHD and autism are double-burdened with a genetic risk of receiving both diagnoses, whereas people who only have one of the diagnoses for the most part only bear the genetic risk variants for this one condition.

"This means, for example, that people with both diagnoses have an equally large load of ADHD genetic factors as people who only have ADHD, and at the same time, the same large load of autism genetic factors as people who only have autism. So it makes perfect biological sense that some people have both diagnoses," says Anders Børglum.

The researchers analyze large datasets of genetic profiles to learn more about diseases and developmental disorders. This can make it possible to create more precise diagnoses and earlier interventions and ensure that the individual patient receives the right treatment.

"The autism diagnosis is typically made before an ADHD diagnosis. So if, for example, the person is also hyperactive and finds it difficult to concentrate, this may well be slightly drowned out by the autism symptoms, and we may not see the ADHD challenges," explains Anders Børglum.

"But if we have a genetic study of a person with an autism diagnosis, and we see a major genetic load of ADHD genetics, then it may be that we should monitor that person a bit more closely. In this way, we can become quicker to spot the development and give the family good tools to handle this diagnosis, too."

A few years ago - due to an official diagnosis hierarchy - it was not in principle possible to diagnose ADHD in a person who had autism, he says.

"But now we have shown that people with both diagnoses are in fact double burdened with the genetic risk of both developmental disorders. There is thus a clear biological difference between whether you have both diagnoses or just one. The study is, therefore, a strong biological argument for the revised diagnostic guidelines, e.g., in the American Diagnosis and Classification system for Mental Disorders (DSM-5), where it is now possible for the same person to receive both diagnoses," says Anders Børglum.

"This is the first step. Here and now, the study is relevant because it helps better to understand the causes of the two developmental disorders. In the long term, this can form the basis for better diagnostics and treatment."

Behind the Research Results

The study examines genetic variations in the genomes of 34,462 people diagnosed with Autism Spectrum Disorder and/or ADHD, and 41,201 control subjects without these diagnoses (a so-called GWAS, genome-wide association study). 8.9 million genetic variants have been examined for each person, spread across the entire genome.

By correlating the genetic results with data from the genes' expression in different regions of the brain and brain cells, e.g., in a so-called Brain Transcriptome-Wide Association Study (TWAS), the researchers can examine the consequences of various genetic risk variants.

The researchers obtain more information about the significance of the genetic risk variants by comparing the results of the autism/ADHD analyses with the results of genetic studies of other mental disorders and general traits, such as cognitive functions and the volume of brain regions.

About the Study

The study is headed by the Danish iPSYCH researchers with many international partners, including the Psychiatric Genomics Consortium (PGC) and the Broad Institute of MIT and Harvard. iPSYCH is primarily financed by the Lundbeck Foundation.

Attribution/Source(s): This peer reviewed publication was selected for publishing by the editors of Disabled World (DW) due to its relevance to the disability community. Originally authored by Professor Anders Børglum, Aarhus University, Department of Biomedicine. and published on 2022/10/04, this content may have been edited for style, clarity, or brevity.