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Meta-Analysis Detects 27 Genetic Variants That Increase ADHD Risk
A genome-wide association study meta-analysis has identified 27 loci in the human genome, more than double the amount detected in previous studies, that increase the risk of attention-deficit/hyperactivity disorder (ADHD). An international team published its findings in Nature Genetics.
“This emphasizes that ADHD should be seen as a brain developmental disorder, and that this is most likely influenced by genes that have a major impact on the brain’s early development,” said first and corresponding study author Ditte Demontis, PhD, a professor in the Aarhus University Department of Biomedicine in Denmark.
Related: In how many settings must ADHD symptoms be present for proper diagnosis?
The meta-analysis included more than 6 million genetic variants in 38,691 people with ADHD and 186,843 people without ADHD. Data stemmed from the Danish iPSYCH cohort, deCODE Genetics in Iceland, and the Psychiatric Genomics Consortium.
When researchers combined the 27 ADHD risk variants with existing data on gene expression in different tissues, cell types, and brain development stages, they found genes involved in ADHD have a high level of expression in a range of brain tissues as early as the embryonic stage of development.
The variants that increase the risk of ADHD mostly affect genes expressed in neurons, especially dopaminergic neurons, according to the research team.
“This is interesting because dopamine plays a role in relation to the reward response in the brain, and because a frequently used form of ADHD medicine works by increasing the concentration of dopamine in different brain regions,” said Dr Demontis. “Our results indicate that the imbalance in dopamine in the brains of people with ADHD is partly attributable to genetic risk factors.”
In an independent dataset of 4973 people who had undergone extensive neuro-cognitive testing, researchers found reduced reading and mathematical abilities, reduced attention, and reduced short-term memory in participants with an increased load of the ADHD risk variants identified in the study.
“The results increase our knowledge of the biological mechanisms underlying ADHD, and they point to specific genes, tissues, and cell types involved in ADHD,” said Dr Demontis. “This knowledge can be used as a starting point for further studies of the disease mechanisms and identification of new drug targets.”
Advanced statistical models estimated as many as 7300 genetic variants may influence ADHD risk, among which 84% and 98% are likely shared with other psychiatric disorders, according to the study.
“We have only mapped a small fraction of the common variants that influence ADHD — just 27 of the 7300 that potentially exist,” said Dr Demontis. “So there is a need for larger genetic studies.”
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