Polygenic Risk Scores Forecast Some ADHD Symptoms

Isabella Vainieri

New research sheds light on the link between polygenic genetic risk scores (PRS) and certain symptoms associated with attention deficit/hyperactivity disorder (ADHD).

A team, led by Isabella Vainieri, Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, used ADHD samples to develop polygenic risk scores for ADHD to test whether genetic variants that contribute to ADHD also influence attention regulation and response inhibition, cognitive functions that show strong associations with ADHD.

Genome-Wide Association Studies

Recently, researchers identified 12 independent loci significantly associated with ADHD in a genome-wide association study. However, polygenic risk scores derived from the genome-wide association study could be useful in assessing genetic overlap between ADHD and other traits.

In the current study, the investigators were able to capture the cognitive functions using reaction time variability (RTV) and commission errors (CE).

In the discovery genome-wide association study there was a total of 19,099 ADHD cases with 34,194 control participants. The combined target sample included 845 individuals with ADHD between 8-40 years old. Reaction time variability and commission errors were available from reaction time and response inhibition tasks and ADHD polygenetic risk scores were calculated from the genome-wide association study using a leave-one-study-out approach.

Taking a New Approach

The investigators used regression analyses to determine whether ADHD polygenic risk scores were linked to commission errors and reaction time variability and used random effect meta-analyses to combine the results across different international sites.

The research team found after combining the studies in the meta-analyses, the results were significant for reaction time variability (R₂ = 0.011; β = 0.088; P = 0.02). However, the results were not significant for commission errors (R₂ = 0.011; β = 0.013; P = 0.732).

In addition, there was no significant association found between ADHD polygenic risk scores and reaction time variability or commission errors in any sample individually (P >0.10).

“We detected a significant association between PRS for ADHD and RTV (but not CE) in individuals with ADHD, suggesting that common genetic risk variants for ADHD influence attention regulation,” the authors wrote.

Building on Past Research

In previous general population sample studies, researchers have found ADHD polygenic risk scores are linked to a number of psychiatric and somatic disorders and traits, including depression, anxiety, neuroticism, irritability, childhood internalizing and externalizing symptoms, obesity-related phenotypes, and smoking.

Polygenic risk scores yield an estimate of the genetic propensity to ADHD at an individual level. This can be used to investigate shared genetic etiology between ADHD and other phenotypes.

However, only a handful of population-based studies have explored the cognitive phenotypes associated with ADHD using polygenic approaches. The few studies that have focused on this link have provided initial evidence on the association between polygenic risk scores for ADHD and lower general cognitive ability, educational attainment, and working memory, but not inhibition impairments.

In addition, evidence from clinically diagnosed samples of ADHD are even more limited.

The study, “Polygenic association between attention-deficit/hyperactivity disorder liability and cognitive impairments,” was published online in Cambridge Core.