The familial co-aggregation of ASD and ADHD: a register-based cohort study

Abstract

Autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD) frequently co-occur. The presence of a genetic link between ASD and ADHD symptoms is supported by twin studies, but the genetic overlap between clinically ascertained ASD and ADHD remains largely unclear. We therefore investigated how ASD and ADHD co-aggregate in individuals and in families to test for the presence of a shared genetic liability and examined potential differences between low- and high-functioning ASD in the link with ADHD. We studied 1 899 654 individuals born in Sweden between 1987 and 2006. Logistic regression was used to estimate the association between clinically ascertained ASD and ADHD in individuals and in families. Stratified estimates were obtained for ASD with (low-functioning) and without (high-functioning) intellectual disability. Individuals with ASD were at higher risk of having ADHD compared with individuals who did not have ASD (odds ratio (OR)=22.33, 95% confidence interval (CI): 21.77-22.92). The association was stronger for high-functioning than for low-functioning ASD. Relatives of individuals with ASD were at higher risk of ADHD compared with relatives of individuals without ASD. The association was stronger in monozygotic twins (OR=17.77, 95% CI: 9.80-32.22) than in dizygotic twins (OR=4.33, 95% CI: 3.21-5.85) and full siblings (OR=4.59, 95% CI: 4.39-4.80). Individuals with ASD and their relatives are at increased risk of ADHD. The pattern of association across different types of relatives supports the existence of genetic overlap between clinically ascertained ASD and ADHD, suggesting that genomic studies might have underestimated this overlap.

Figure 1

Flow diagram of the study population. The flow diagram illustrates how the study population was defined. In each cohort of relatives, the reported numbers refer to the number of relative pairs.

Figure 2

Within-individual and within-family associations between autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). Forest plot illustrating odds ratios (ORs, diamonds) and 95% confidence interval (CI, bars) expressing the association between ASD and ADHD obtained from the within-individual analysis performed in the whole sample and from the within-family analyses performed in the cohorts of different relatives. All the estimates were adjusted for birth year and sex. The numbers of observations for each cohort are: 1 899 654 for the whole sample (that is, within-individual estimates); 8360 for monozygotic twins; 25 310 for dizygotic twins; 1 829 696 for full siblings; 273 924 for maternal half siblings; 269 004 for maternal half siblings; 5 580 328 for full cousins; and 1 251 584 for half cousins.