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Genetic risk for Attention Deficit/Hyperactivity Disorder contributes to neurodevelopmental traits in the general population

Martin, Joanna, Hamshere, Marian L., Stergiakouli, Evangelia, O'Donovan, Michael Conlon and Thapar, Anita 2014. Genetic risk for Attention Deficit/Hyperactivity Disorder contributes to neurodevelopmental traits in the general population. Biological Psychiatry 76 (8) , pp. 664-671. 10.1016/j.biopsych.2014.02.013

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Abstract

Background Attention-deficit hyperactivity disorder (ADHD) can be viewed as the extreme end of traits in the general population. Epidemiological and twin studies also suggest that ADHD frequently co-occurs with and shares genetic susceptibility with autism spectrum disorder (ASD)/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. Method Polygenic risk scores were calculated in the Avon Longitudinal Study of Parents and Children (ALSPAC) population sample (N=8,229), 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 also ASD-related measures (pragmatic language abilities and social cognition) in ALSPAC. Polygenic scores were also compared in males and females endorsing any (≥1) ADHD item (N=3,623). Results ADHD polygenic risk showed a positive association with ADHD (hyperactive-impulsive: p=0.0039; inattentive: p=0.037) traits. ADHD polygenic risk was also negatively associated with pragmatic language abilities (p=0.037), but not with social cognition (p=0.43). In children with a rating ≥1 for ADHD traits, females had a higher polygenic score than males (p=0.003). 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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Neuroscience and Mental Health Research Institute (NMHRI)
Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
R Medicine > RJ Pediatrics
Uncontrolled Keywords: Avon Longitudinal Study of Parents and Children (ALSPAC); Attention Deficit Hyperactivity Disorder; Autism Spectrum Disorder; Social-Communication; Pragmatic Language; Genetics
Additional Information: Online publication date: 25 February 2014.
Publisher: Elsevier
ISSN: 0006-3223
Funders: Wellcome Trust, MRC
Date of First Compliant Deposit: 30 March 2016
Date of Acceptance: 13 February 2014
Last Modified: 15 Jun 2020 07:45
URI: http://orca.cf.ac.uk/id/eprint/58158

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