summary: Researchers have identified 27 new genetic variants associated with the development of ADHD.
sauce: Aarhus University
Why do some people get ADHD and others don’t? And how early in life are the seeds of ADHD planted?
Researchers at Aarhus University are trying to answer this question in a large study. natural genetics.
Working with domestic and international partners, researchers studied over 6 million genetic mutations in 38,691 people with ADHD and 186,843 people without ADHD. This allowed us to identify 27 genetic risk variants for common neurodevelopmental disorders.
Risk genes expressed in brain and nerve cells
This study is landmark, among other things, because it found more than double the risk variants identified in previous studies.
The term “genetic variant” refers to specific variations in the DNA code. In this case, a variant observed more frequently in people with her ADHD than in those without a diagnosis. DNA variants, for example, affect the degree to which a gene is expressed, which in turn affects the amount of protein encoded by that gene.
By associating genetic variants (that is, variations in DNA) with specific genes, researchers have gained new knowledge about the tissues and cell types that are particularly affected in individuals with ADHD. This study is based on data from the Danish iPSYCH cohort, Icelandic deCODE Genetics, and the Psychiatric Genomics Consortium.
The researchers then combined existing data and results on gene expression in different tissues, cell types, and stages of brain development, and found that genes implicated in ADHD are at particularly high levels in a wide range of brain tissues and early stages of the brain. was found to occur in Development – in fact already in the early stages.
“This underscores that ADHD should be viewed as a developmental brain disorder and that it is most likely influenced by genes that have a large impact on early brain development,” said Aarhus University. said Professor Ditte Demontis of the Biomedical School. First author of the study.
Additionally, researchers found that genetics that increase the risk of ADHD specifically affect genes expressed in neurons, especially dopaminergic neurons.
“This is interesting because dopamine plays a role in relation to reward responses in the brain, and frequently used ADHD medications work by increasing concentrations of dopamine in different areas of the brain. “Our results show that the dopamine imbalance in the brains of people with ADHD is partly due to genetic risk factors,” said Ditte Demontis.
Associated with poor concentration and short-term memory
ADHD is affected by many common genetic mutations, each of which slightly increases risk, he said.
In fact, with the help of advanced statistical models, researchers estimate that there are about 7,300 common genetic mutations that increase ADHD risk. It is of particular interest that it also affects other psychiatric disorders such as autism, depression and schizophrenia.
It has been previously shown that ADHD risk variants can affect a person’s cognitive performance.
To investigate this further, the researchers analyzed data from an independent dataset of 4,973 individuals who underwent extensive neurocognitive testing. By using information from a new study about which variants increase his risk of ADHD, they found that in an independent dataset, the increased ADHD risk variant burden in an individual’s genome correlated with reading and mathematics. found to be associated with decreased mental performance and reduced alertness. short term memory.
“This result enhances our knowledge of the biological mechanisms underlying ADHD and points to the specific genes, tissues, and cell types involved in ADHD. It can be used as a starting point for identifying new drug targets,” explains Ditte Demontis.
And this study must be followed up, she stresses.
“We’ve only mapped a small fraction of the common variants that affect ADHD, only 27 of the 7,300 that are potentially present, so larger-scale genetic studies are needed,” she says. .
The Way Forward for International Interdisciplinary Collaboration
Large-scale international collaboration is essential to identify the genetic causes of psychiatric and neurodevelopmental disorders. Because that would require studies of tens or hundreds of thousands of people with these diseases.
As with current ADHD research, it involves over 100 researchers with diverse specialties, including genetics, psychiatry, psychology, epidemiology, molecular biology, statistics, bioinformatics, and computer science often
See also
“It’s important to do larger studies with more ADHD patients to better understand the genetic and biological mechanisms,” said Aarhus, the study’s last author. Professor Anders Børglum of the University’s Department of Biomedical Sciences said. He is the head of research for the iPSYCH project in Denmark.
“However, we are embarking on research focused on identifying how genetic risk variants disrupt the biological processes of brain cells (neurons) and how they bind and communicate with each other in the brain. It is also important that for the latter, both brain cells and early developmental stages of the brain, so-called minibrains or brain organoids, are currently being investigated,” he says.
About this ADHD and genetics research news
author: press office
sauce: Aarhus University
contact: Press Office – Aarhus University
image: image is public domain
Original research: closed access.
“Genome-wide analysis of ADHD identifies 27 risk loci, refines genetic architecture, and reveals involvement of several cognitive domains” by Ditte Demontis et al. natural genetics
overview
Genome-wide analysis of ADHD identifies 27 risk loci, refines genetic architecture, and reveals involvement of several cognitive domains
Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder with a major genetic component. Here we present a meta-analysis of genome-wide association studies of ADHD involving 38,691 individuals with ADHD and his 186,843 controls.
We identified 27 genome-wide significant loci and highlighted 76 potential risk genes that are particularly abundant among those expressed in early brain development. Overall, ADHD genetic risk was associated with several brain-specific neuronal subtypes and dopaminergic neurons in the midbrain.
In exome sequencing data from 17,896 individuals, we identified an increased burden of rare protein truncation variants in ADHD. This is a set of risk genes rich in common causative variants, potentially implicated. SORCS3 ADHD with both common and rare variants. Bivariate Gaussian mixture modeling estimates that 84–98% of variants affecting ADHD are shared with other psychiatric disorders.
Furthermore, common variant ADHD risk was associated with complex cognitive deficits such as verbal reasoning and various executive functions including attention.
