Polygenic association between attention-deficit/hyperactivity disorder liability and cognitive impairments

Area of Science:

• Psychiatry
• Genetics
• Neuroscience

Background:

• Genome-wide association studies (GWAS) have identified genetic loci associated with Attention-Deficit/Hyperactivity Disorder (ADHD).
• Polygenic Risk Scores (PRS) can quantify genetic overlap between ADHD and other traits.
• Cognitive functions like attention regulation and response inhibition are strongly linked to ADHD.

Purpose of the Study:

• To investigate whether genetic variants contributing to ADHD also influence attention regulation and response inhibition.
• To utilize ADHD PRS derived from a large GWAS to examine their association with cognitive functions in ADHD samples.

Main Methods:

• ADHD PRS were calculated using a leave-one-study-out approach from a discovery GWAS (19,099 cases, 34,194 controls).
• Regression analyses were performed to assess the association between ADHD PRS and measures of attention regulation (Reaction Time Variability - RTV) and response inhibition (Commission Errors - CE) in a combined sample of 845 individuals with ADHD.
• Results were meta-analyzed across international sites using random effect models.

Main Results:

• A significant association was found between ADHD PRS and RTV (p=0.02), indicating that genetic variants for ADHD influence attention regulation.
• No significant association was detected between ADHD PRS and commission errors (p=0.732), suggesting no link to response inhibition in this study.
• Individual sample analyses did not yield significant associations (p > 0.10).

Conclusions:

• Common genetic risk variants for ADHD are associated with attention regulation, as indicated by the link between ADHD PRS and RTV.
• The study did not find evidence that these common genetic risk variants for ADHD influence response inhibition (CE).
• These findings highlight the role of shared genetic factors in the neurobiological underpinnings of ADHD and attention regulation.