28 November 2018

A major international collaboration headed by researchers from the Danish iPSYCH project, the Broad Institute of Harvard and MIT, and the Psychiatric Genomics Consortium has - for the first time - identified genetic variants which 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 had yet to deliver 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 search for such genetic risk variants for ADHD has spanned decades, without obtaining robust results. This time, through the large international collaboration in the Psychiatric Genomics Consortium and the population-wide approaches of the Danish iPSYCH consortium, the researchers were able to succeed in describing the first risk variants and genes for ADHD from genome-wide approaches. ‘International collaboration at a world-wide scale enabled this result – team science is really essential to make progress in finding the genes for psychiatric disorders.’ says Professor Barbara Franke, who recently became one of the leaders of the Psychiatric Genomics Consortium’s ADHD Working Group, ‘especially for ADHD, which is by some still not believed to be a real disorder, identifying the underlying genes and biological mechanisms is of great importance’.
 
These genetic discoveries provide new insights into the biology behind developing ADHD. For example, some of the genes have 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 typically regulate how much a gene is expressed, and that the genes affected are primarily expressed in the brain.

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 ADHD symptom levels in the general population. The researchers discovered that the same genetic variants that give rise to an ADHD diagnosis also affect inattention and hyperactivity/impulsivity in the general population.

The risk variants are 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.

The researchers also studied the genetic overlap of ADHD with other diseases and traits. They found a strong negative genetic correlation between ADHD and education. This means that, on average, genetic variants which increase the risk of ADHD also influence performance in the education system negatively for people in the general population who carry these variants without having ADHD.

Conversely, the study found a positive correlation between ADHD and obesity, increased BMI and type-2 diabetes, which is to say that variants that increase the risk of ADHD also increase the risk of overweight and type-2 diabetes in the population.
 
The study is an important foundation for further research into ADHD. Researchers can now target their studies to achieve a deeper understanding of how the risk genes affect the development of ADHD. When the pieces of that puzzle come together in this way, researchers will be able to improve the diagnosis and treatment of ADHD.

The research results – more information

  • Type of study: The genetic risk variants for ADHD can be found by screening the entire genome in a large number of people with ADHD and comparing them with healthy individuals. If a genetic variant is found to be sufficiently more common in people with ADHD compared with healthy individuals, the researchers can conclude that the variant most likely affects the risk of suffering from the disorder. A total of 20,183 people with ADHD and 35,191 control subjects were examined, including a substantial contribution from iPSYCH which collected genetic information from 14,584 people with ADHD and 22.492 people in a control group.
  • External funding: The Lundbeck Foundation and several international foundations including the Stanley Foundation, NIH/NIMH and the EU.
  • Partners: Many ADHD researchers from around the world who are organised in The Psychiatric Genomics Consortium.
  • Read the complete scientific article in Nature Genetics.

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