The Genetic Overlap of Attention-Deficit/Hyperactivity Disorder and Autistic-like Traits: an Investigation of Individual Symptom Scales and Cognitive markers

Abstract

Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorders (ASDs) frequently co-occur. However, due to previous exclusionary diagnostic criteria, little is known about the underlying causes of this covariation. Twin studies assessing ADHD symptoms and autistic-like traits (ALTs) suggest substantial genetic overlap, but have largely failed to take into account the genetic heterogeneity of symptom subscales. This study aimed to clarify the phenotypic and genetic relations between ADHD and ASD by distinguishing between symptom subscales that characterise the two disorders. Moreover, we aimed to investigate whether ADHD-related cognitive impairments show a relationship with ALT symptom subscales; and whether potential shared cognitive impairments underlie the genetic risk shared between the ADHD and ALT symptoms. Multivariate structural equation modelling was conducted on a population-based sample of 1312 twins aged 7-10. Social-communication ALTs correlated moderately with both ADHD symptom domains (phenotypic correlations around 0.30) and showed substantial genetic overlap with both inattention and hyperactivity-impulsivity (genetic correlation = 0.52 and 0.44, respectively). In addition to previously reported associations with ADHD traits, reaction time variability (RTV) showed significant phenotypic (0.18) and genetic (0.32) association with social-communication ALTs. RTV captured a significant proportion (24 %) of the genetic influences shared between inattention and social-communication ALTs. Our findings suggest that social-communication ALTs underlie the previously observed phenotypic and genetic covariation between ALTs and ADHD symptoms. RTV is not specific to ADHD symptoms, but is also associated with social-communication ALTs and can, in part, contribute to an explanation of the co-occurrence of ASD and ADHD.

Keywords: Attention-deficit/hyperactivity disorder (ADHD); Autism spectrum disorders (ASDs); Autistic-like traits (ALTs); Genetics; Reaction time variability (RTV).

Fig. 1

Correlated factor solution of the full ACE Cholesky Decomposition. Note: Significant parameters are indicated with solid lines; non-significant parameters in dotted lines; Abbreviations: HYP-IMP Hyperactivity-impulsivity, INATT inattention, ALT-SOC social-communication autistic-like trait subscale, ALT-NON non-social autistic-like trait subscale, RTV reaction time variability, CE commission errors, G broad-sense genetic influences, C shared environmental influences, E individual-specific environmental influences; Model presented for one twin only for ease of presentation

Fig. 2

Broad-sense genetic and individual-specific environmental parameter estimates from the reduced three-variable Cholesky model. Note: unstandardised parameter estimates; significant parameters are indicated with solid lines and non-significant parameters with dotted lines; Abbreviations: RTV reaction time variability, INATT inattention, ALT-SOC social-communication autistic-like traits, G broad-sense genetic influences, E individual-specific environmental influences; Model presented for one twin only for ease of presentation and for the etiological factors that contributed to covariation between all traits (i.e., G and E)