Sunday , October 24 2021

First risk genes for ADHD found – ScienceDaily



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A major international collaboration led by researchers from the Danish iPSYCH project, the Broad Institute of Harvard and MIT, Massachusetts General Hospital, SUNY Upstate Medical University, and the Psychiatric Genomics Consortium has first 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 capture up to 75% of the risk. Until now, the search for these genes has yet to provide clear results. Researchers from the Psychiatric Genomics Consortium have compared genetic variation across the entire genome for over 20,000 people with ADHD and 35,000 who do not suffer from it – finding twelve locations where people with a particular genetic variant have an increased risk of ADHD compared to those who do not have the variant.

The results of the study have just been published in the scientific journal Nature Genetics.

"The large amount of data enabled us to find, for the first time, locations in the genome where people with ADHD stand out from those who are healthy.The search for such genetic risk variants for ADHD has spanned decades but without getting robust results. This time we really expanded the number of study subjects substantially, increasing the power to achieve conclusive results significantly. Specifically, we included a large number from the Danish iPSYCH cohort representing more than 2/3 of the total international study sample, "explains Associate Professor Ditte Demontis from Aarhus University.

She along with Raymond Walters of Massachusetts General Hospital are the leading authors of the study, working as part of the ADHD group of the Psychiatric Genomics Consortium, an international consortium of researchers dedicated to discovering the genetics factors that lead to ADHD.

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

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

The same genes affect impulsivity in healthy people

In the study, the researchers have also compared the new results with those from a genetic study of continuous measures of ADHD behaviors in the general population. The researchers discovered that the same genetic variations that give rise to an ADHD diagnosis also affect inattention and impulsivity in the general population.

"The risk variants are thus widespread in the population. The more risk variants you have, the greater your tendency to have ADHD-like characteristics will be as well as your risk of developing ADHD," says Professor Anders Børglum from Aarhus University. He is research head at iPSYCH and one of the leading researchers who conducted the study along with Professor Stephen Faraone of SUNY Upstate Medical University and Benjamin Neale of Massachusetts General Hospital and the Broad Institute.

"We also studied the genetic overlap with other diseases and traits, with a strong negative genetic correlation between ADHD and education, which means that an average genetic variant that increases the risk of ADHD also influences performance in the education system negatively for people in the general population who carry these variants without having ADHD, "says Ditte Demontis.

Conversely, the study found a positive correlation between ADHD and obesity, increased BMI and type-2 diabetes, which is to say that variations that increase the risk of ADHD also increase the risk of overweight and type-2 diabetes in the population.

"These findings and results also emphasize the importance of collaboration to advance discovery efforts. It is only through data sharing and working together that we were able to find these regions of the genome," explains Dr. Benjamin Neale.

"The new findings mean that we now – after many years of research – finally have robust genetic findings that can inform about the underlying biology and what role genetics plays in the diseases and traits often associated with ADHD. Study is an important foundation for further research into ADHD. We can now target our studies, so we can achieve a thorough understanding of how the risk genes affect the development of ADHD with the aim of ultimately providing better help for people with ADHD, "said Anders Børglum.

"We have laid the foundation for future work that will clarify how genetic risks combine with environmental risks to cause ADHD. When the pieces of this puzzle come together, researchers will be able to improve the diagnosis and treatment of ADHD," says Professor Stephen Faraone.

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Materials provided by Aarhus University. Original written by Annette Bang Rasmussen. Note: Content may be edited for style and length.

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