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

Joanna Martin, Marian L Hamshere, Evangelia Stergiakouli, Michael C O'Donovan, Anita Thapar

Research output: Contribution to journalArticle (Academic Journal)peer-review

95 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)664-71
Number of pages8
JournalBiological Psychiatry
Volume76
Issue number8
DOIs
Publication statusPublished - 15 Oct 2014

Keywords

  • Adolescent
  • Attention Deficit Disorder with Hyperactivity
  • Child
  • Child Development Disorders, Pervasive
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Longitudinal Studies
  • Male
  • Phenotype
  • Psychiatric Status Rating Scales
  • Risk Factors

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