Summary: Genetic variants that influence aggressive behaviour in children with ADHD largely overlap with the genetic factors that affect aggression in the wider population.
Source: Aarhus University
An international research collaboration led by investigators from the Danish iPSYCH consortium has identified genetic variants that raise the risk of aggressive behaviour in children with attention-deficit/hyperactivity disorder (ADHD). The team also found that many of these genetic influences are shared with aggression measured in children from the general population.
This study is the first to pinpoint specific genomic locations that are associated with ADHD combined with disruptive behaviour disorders (DBDs)—a group of childhood psychiatric conditions marked by persistent antisocial or aggressive behaviour. Around 20–30% of children diagnosed with ADHD also meet criteria for DBDs, and the new findings help clarify some of the biological factors that increase risk for this comorbid presentation.
The researchers performed a genome-wide association study (GWAS) using genetic data from 3,802 children diagnosed with ADHD and DBDs and 31,305 control participants without those diagnoses. The analysis identified three genome-wide significant loci on chromosomes 1, 7, and 11 that are associated with the combined ADHD+DBDs phenotype. One variant on chromosome 11, highlighted in the study, appears to be a robust risk signal for ADHD with disruptive behaviours across populations.
Beyond locating risk variants, the study shows that aggressive behaviour within the ADHD population is partly heritable and influenced by many common genetic variants. The authors report a higher single-nucleotide polymorphism (SNP) heritability for ADHD with DBDs (h2_SNP = 0.34) compared with ADHD without DBDs (h2_SNP = 0.20), indicating a greater contribution from common genetic variation to the comorbid condition.
A cross-population meta-analysis that included a Chinese cohort reinforced the role of the chromosome 11 locus as a strong and consistent risk factor (rs7118422, P = 3.15×10−10, OR = 1.17). The study also found very high genetic correlations between ADHD+DBDs and measures of aggressive (rg = 0.81) and antisocial behaviour (rg = 0.82), and an increased polygenic burden of variants linked to both ADHD and aggression in children with ADHD+DBDs compared with children who have ADHD alone.
“We compared our results with a large genetic study of aggression in children without psychiatric diagnoses and found striking overlap,” says Ditte Demontis, associate professor at Aarhus University and a lead author on the study. “In other words, many of the genetic factors that increase the risk of aggression in children with ADHD are the same as those that influence aggression in the general population. Children with ADHD and DBDs carry a higher load of these common risk variants.”
ADHD and DBDs are complex conditions in which both inherited genetic factors and environmental influences contribute to risk. The genetic architecture revealed by this GWAS suggests that many common variants, each with a small effect, combine to influence whether a child develops ADHD with disruptive behaviours. The specific loci identified in this study represent an initial step toward unraveling biological pathways involved in aggression and comorbid ADHD.
“The variants we report are likely only the tip of the iceberg,” Demontis adds. “Larger studies and more diverse samples will be needed to capture the full spectrum of genetic risk and to translate these insights into biological mechanisms or potential targets for intervention.”
The research approach and implications
This research used a GWAS framework, scanning millions of genetic variants across the genome to detect those that are more frequent in cases (ADHD+DBDs) than in controls. By combining data from multiple cohorts and ancestries, the researchers increased statistical power to detect modest but reliable signals. The findings improve our understanding of how common genetic variation contributes to aggressive and antisocial behaviours when they co-occur with ADHD, and they highlight the value of studying comorbid presentations as distinct genetic profiles within psychiatric disorders.
About this genetics and ADHD research news
Source: Aarhus University
Contact: Ditte Demontis – Aarhus University
Image: The image is in the public domain
Original Research: Open access. “Risk variants and polygenic architecture of disruptive behavior disorders in the context of attention-deficit/hyperactivity disorder” by Ditte Demontis, Raymond K. Walters, Veera M. Rajagopal, Irwin D. Waldman, Jakob Grove, Thomas D. Als, Søren Dalsgaard, Marta Ribasés, Jonas Bybjerg-Grauholm, Maria Bækvad-Hansen, Thomas Werge, Merete Nordentoft, Ole Mors, Preben Bo Mortensen, ADHD Working Group of the Psychiatric Genomics Consortium (PGC), Bru Cormand, David M. Hougaard, Benjamin M. Neale, Barbara Franke, Stephen V. Faraone & Anders D. Børglu. Nature Communications
Abstract (summary)
Risk variants and polygenic architecture of disruptive behavior disorders in the context of attention-deficit/hyperactivity disorder
Attention-Deficit/Hyperactivity Disorder (ADHD) frequently occurs with disruptive behaviour disorders (DBDs). This GWAS meta-analysis of ADHD comorbid with DBDs (3,802 cases and 31,305 controls) identified three genome-wide significant loci on chromosomes 1, 7, and 11. A meta-analysis including a Chinese cohort supports the chromosome 11 locus as a trans-ancestry risk signal (rs7118422, P = 3.15×10−10, OR = 1.17). The study reports higher SNP heritability for ADHD+DBDs (h2SNP = 0.34) compared with ADHD without DBDs (h2SNP = 0.20), strong genetic correlations with aggression and antisocial behaviour, and an increased polygenic burden of variants associated with both ADHD and aggression in the comorbid group. These results suggest an elevated load of common risk variants in ADHD+DBDs, partly driven by variants related to aggressive behaviour.