Genetic risk for attention-deficit/hyperactivity disorder contributes to neurodevelopmental traits in the general population

Abstract

Background: Attention-deficit/hyperactivity disorder (ADHD) can be viewed as the extreme end of traits in the general population. Epidemiological and twin studies suggest that ADHD frequently co-occurs with and shares genetic susceptibility with autism spectrum disorder (ASD) and ASD-related traits. The aims of this study were to determine whether a composite of common molecular genetic variants, previously found to be associated with clinically diagnosed ADHD, predicts ADHD and ASD-related traits in the general population.

Methods: Polygenic risk scores were calculated in the Avon Longitudinal Study of Parents and Children (ALSPAC) population sample (N = 8229) based on a discovery case-control genome-wide association study of childhood ADHD. Regression analyses were used to assess whether polygenic scores predicted ADHD traits and ASD-related measures (pragmatic language abilities and social cognition) in the ALSPAC sample. Polygenic scores were also compared in boys and girls endorsing any (rating ≥ 1) ADHD item (n = 3623).

Results: Polygenic risk for ADHD showed a positive association with ADHD traits (hyperactive-impulsive, p = .0039; inattentive, p = .037). Polygenic risk for ADHD was also negatively associated with pragmatic language abilities (p = .037) but not with social cognition (p = .43). In children with a rating ≥ 1 for ADHD traits, girls had a higher polygenic score than boys (p = .003).

Conclusions: These findings provide molecular genetic evidence that risk alleles for the categorical disorder of ADHD influence hyperactive-impulsive and attentional traits in the general population. The results further suggest that common genetic variation that contributes to ADHD diagnosis may also influence ASD-related traits, which at their extreme are a characteristic feature of ASD.

Keywords: Attention-deficit/hyperactivity disorder; Avon Longitudinal Study of Parents and Children (ALSPAC); autism spectrum disorder; genetics; pragmatic language; social communication.

Figure 1

Histograms of attention-deficit/hyperactivity disorder and social communication traits. ADHD, attention-deficit/hyperactivity disorder; CCC, Children’s Communication Checklist; SCDC, Social and Communication Disorders Checklist.

Figure 2

Mean z scores of ADHD and social communication outcomes, displayed by diagnostic group. Error bars represent SEM. ⁎Scores reversed. ADHD, attention-deficit/hyperactivity disorder; ASD, autism spectrum disorder; CCC PL, Children’s Communication Checklist pragmatic language; H-I, hyperactive-impulsive; I, inattentive; SCDC, Social and Communication Disorders Checklist.