Thursday , February 25 2021

Researchers identify the first variants of genetic risk for ADHD

The major international collaboration led by researchers from the Danish iPSYCH project, the Broad Institute of Harvard and MIT, the Massachusetts General Hospital, SUNY Upstate Medical University and the Psychiatric Genomic Consortium for the first time identified genetic variants that increase the risk of ADHD. The new findings provide a completely new insight into the biology behind ADHD.

Our genes are very important for the development of mental disorders – including ADHD, where genetic factors include up to 75% risk. So far, the search for these genes has not yet yielded clear results. Researchers from the psychiatric genomic consortium compute the genetic variation of the whole genome for more than 20,000 people with ADHD and 35,000 people who do not suffer this – finding twelve sites where people with a particular genetic variant have an increased risk of ADHD compared to those who do not variants.

The results of the study were just published in a scientific journal Natural genetics.

"A large amount of data has allowed us for the first time a site in the genome where people with ADHD stand out from those who are healthy." The search for such genetic variants of risk for ADHD has been for decades, but without obtaining robust results, this time we have really expanded the number of study subjects significantly, increasing the power to get the final results significantly. We have specifically included a large number from the Danish iPSYCH cohort that represents more than 2/3 of the overall international study sample, "explains Associate Professor Ditte Demontis of the Aarhus University.

She and Raymond Walters from the Massachusetts General Hospital are leading authors of the study, working as part of the ADHD group of psychiatric genomics of the consortium, an international consortium of researchers dedicated to the discovery of genetic factors that induce ADHD.

These genetic discoveries provide new insights into the biology behind the development of ADHD. For example, some of the genes have the significance of how brain cells communicate with one another, while others are important for cognitive functions such as language and learning.

"Overall, the results show that the risk variants usually regulate how much the gene is expressed, and that genes that are affected are primarily expressed in the brain," explains Professor Demontis.

The same genes affect the impulsivity of healthy people

In the research, the researchers compared new findings with those from the genetic study of continuous measures of ADHD behavior in the general population. Researchers have found that the same genetic variants that lead to ADHD diagnosis also affect the negligence and impulse in the general population.

"The risk variants are so widespread in the population. The more risk variations you have, the greater your tendency to have features like ADHD, and your risk of developing ADHD," says Professor Anders Børglum of the Aarhus University. The research leader is iPSYCH and one of the leading researchers who led the study together with professors Stephen Faraone from Medical University SUNY Upstate and Benjamin Neale from the General Hospital of Massachusetts and Broad Institute.

"We also studied the genetic overlap with other diseases and traits, through which we found a strong negative genetic correlation between ADHD and education, which means that on average genetic variants that increase the risk of ADHD also negatively affect the performance in the education system in the general population which carries these variants without ADHD, "says Ditte Demontis.

In contrast, the study found a positive correlation between ADHD and obesity, increased BMI and type 2 diabetes, which means that variants that increase the risk of ADHD also increase the risk of overweight and type 2 diabetes in the population.

"These findings and results highlight the importance of collaboration to improve detection efforts, only through data exchange and collaborative work, so we have succeeded in finding those regions of the genome," explains Dr Benjamin Neale.

"New findings mean that now – after many years of research – they have finally had robust genetic findings that can inform about basic biology and what role genetic factors in diseases and characteristics that often work with ADHD are an important basis for further ADHD research Now we can direct our studies, so we can achieve a deeper understanding of how risk genes affect the development of ADHD in order to ultimately provide better assistance to people with ADHD, "says Anders Børglum.

"We laid the foundations for future work that will explain how genetic risks are combined with environmental risks to trigger ADHD. When pieces of these puzzles meet, researchers will be able to improve the diagnosis and treatment of ADHD," says Professor Stephen Faraone.

Research results – more information

Type of study: Variants of genetic risk for ADHD can be found by examining the entire genome of a large number of people with ADHD and comparing them with healthy individuals. If the genetic variant is found to be more common in people with ADHD compared to healthy individuals, researchers may conclude that the variant most likely affects the risk of distress from the disorder. A total of 20,183 people with ADHD and 35,191 control subjects were examined, including a significant contribution from iPSYCH, which collected genetic information from 14,584 people with ADHD and 22,492 people in the control group.

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