First Genetic Risk Variants of ADHD Identified

November 29, 2018
First Genetic Risk Variants of ADHD Identified
Source: Credit:KatarzynaBialasiewicz/Getty Images

A genome-wide association study (GWAS) published this week confirms what the psychiatric community has theorized for decades—that attention deficit/hyperactivity disorder (ADHD) has a large genetic component. A collaborative, global research team has identified the first genetic variants that increase the risk of ADHD.

Anita Thapar, Ph.D., professor in the division of psychological medicine and clinical neurosciences at the Cardiff University School of Medicine and an author on the study notes, “This study marks a very important step in beginning to understand the genetic and biological underpinnings of ADHD.”

The paper, titled “Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder” published in Nature Genetics reports a genome-wide association meta-analysis of 20,183 individuals diagnosed with ADHD and 35,191 controls that identifies variants in 12 independent loci that contribute to ADHD.

Anders Børglum, Ph.D., professor at the department of biomedicine, Aarhus University, tells GEN, “These new genetic findings provide completely new windows to understanding the biology behind the development of ADHD.” He adds, “For example, some of the implicated genes influence how brain cells communicate with each other, while others are important for cognitive functions such as language and learning.” He notes that, “The risk variants typically regulate how much a gene is expressed, and our results show that the genes affected are primarily expressed in the brain.”

“We identified 12 genomic regions at which people with ADHD differed compared to unaffected individuals, and several of these regions are in or near genes with a known relationship to biological processes involved in healthy brain development,” notes Joanna Martin, Ph.D., research associate in the division of psychological medicine and clinical neurosciences at Cardiff University’s School of Medicine.

The global nature of this study, with collaboration between research groups from Europe, North America, and China, as well as researchers from the Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH) in Denmark, is a meaningful component of the data used in this study. Dr. Thapar notes, “This is a landmark study because it involves patients from all over the world. This large number of patient samples has been lacking for ADHD, meaning our understanding of ADHD genetics has lagged behind physical disorders and other psychiatric disorders like schizophrenia and depression. Thanks in large part to Denmark, this is beginning to change.”

Dr. Børglum explains that in addition to the identified loci, they also “identified more than 40 diseases or traits that have genetic signals significantly overlapping with ADHD, with positive correlations to major depression, overweight, type 2 diabetes, and insomnia.” This finding, says Steve Faraone, Ph.D., distinguished professor of psychiatry and behavioral sciences at SUNY Upstate Medical University, “tells us that there is a fundamental biology shared across these disorders.”

FOXP2, one of the most well-studied genes in language development in humans, is among the genes identified. Also, DUSP6, which is involved in the control of dopaminergic neurotransmission, a process targeted by most common ADHD pharmacological treatments, was one of the genes found. And, SEMA6D, expressed in the brain during the embryonic development, which could play an important role in the creation of neural branches.

ADHD, which affects 5% of children and 2.5% of adults, is a brain disorder, likely involving processes such as formation of connections between nerve cells, regulation of the neurotransmitter dopamine, speech development, and learning. It is marked by an ongoing pattern that may include inattention (wandering off task, lacking persistence, difficulty sustaining focus, and disorganization) and/or hyperactivity-impulsivity (excessive fidgeting, tapping or talking, making hasty actions that may have a high potential for harm.) For people with ADHD, these behaviors can interfere with or reduce the quality of how they function socially, at school, or at work.

The researchers also found that diagnosed ADHD appears to share much of the same genetic background as the general traits of ADHD, like inattention and fidgetiness, that appear in the general population. They compared the genetic risk for diagnosed ADHD with genetic markers associated with traits of ADHD in over 20,000 children and found a high correlation between the two, at around 97%. “The correlation between these rather different definitions of ADHD suggests that clinically diagnosed ADHD may be the severe end of a continuous distribution of symptoms in the general population,” explains Dr. Martin. In short, the study suggests that the more genetic risk variants we have, the greater our risk for developing ADHD.

The vast majority of ADHD genetics is still undiscovered and will require even larger studies. Dr. Faraone says that obtaining more samples is critical, and hopes to have at least 100,000 included in the next study. He guesses that there are many more genes involved in ADHD, adding that there could be up to thousands. Dr. Børglum agrees that the next important step is to “increase sample size as much as possible and include samples from more study subjects with ADHD.” Dr. Thapar adds that they also need to “determine the exact role of these genes in ADHD to help us inform better treatments to support those affected by the condition” which Dr. Børglum agrees is necessary to “point to novel targets for drug development.”

Indeed, ADHD’s lack of known cause and complex array of symptoms lead to a high degree of misunderstanding with many misconceptions. For example, as Dr. Faraone tells GEN, “there is a mythology out there that ADHD kids have bad parents or that American society is just too stressful on them. Or, that ADHD is not a disorder and we use it to pathologize normal kids.” This paper and other research like it will hopefully start to turn the tide by advancing the understanding of why some individuals develop ADHD and insights into the underlying biology. Not only that, but because current treatment options are generally not very effective and often carry side effects, this work will also pave the way for new and better treatments for ADHD.