title: 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.
authors.affiliation: MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Cardiff. Electronic address: thapar@cardiff.ac.uk.
authors.forename: Joanna
authors.initials: J
authors.lastname: Martin
authors.affiliation: MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Cardiff.
authors.forename: Marian L
authors.initials: ML
authors.lastname: Hamshere
authors.affiliation: MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.
authors.forename: Evangelia
authors.initials: E
authors.lastname: Stergiakouli
authors.affiliation: MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Cardiff.
authors.forename: Michael C
authors.initials: MC
authors.lastname: O'Donovan
authors.affiliation: MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Cardiff.
authors.forename: Anita
authors.initials: A
authors.lastname: Thapar
mesh_terms: D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000453:epidemiology / Q000235:genetics*; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000453:epidemiology / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D010641:Phenotype; D011569:Psychiatric Status Rating Scales; D012307:Risk Factors
keywords: Attention-deficit/hyperactivity disorder; Avon Longitudinal Study of Parents and Children (ALSPAC); autism spectrum disorder; genetics; pragmatic language; social communication