Genetic Risk for Attention-Deficit/Hyperactivity Disorder Contributes to Neurodevelopmental Traits in the General Population

• Published in: Biological psychiatry (1969) 2014-10, Vol.76 (8), p.664-671
• Main Authors: Martin, Joanna, Hamshere, Marian L, Stergiakouli, Evangelia, O’Donovan, Michael C, Thapar, Anita
• Format: Article
• Language: English
• Subjects: Adolescent; Archival Report; Attention Deficit Disorder with Hyperactivity - epidemiology; Attention Deficit Disorder with Hyperactivity - genetics; Attention-deficit/hyperactivity disorder; autism spectrum disorder; Avon Longitudinal Study of Parents and Children (ALSPAC); Child; Child Development Disorders, Pervasive - epidemiology; Child Development Disorders, Pervasive - genetics; Female; Genetic Predisposition to Disease; genetics; Genome-Wide Association Study; Genotype; Humans; Longitudinal Studies; Male; Phenotype; pragmatic language; Psychiatric Status Rating Scales; Psychiatry; Risk Factors; social communication
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/j.biopsych.2014.02.013

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.