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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: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Neuroscience and Mental Health Research Institute (NMHRI)
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
Last Modified: 16 Mar 2019 22:54
URI: http://orca.cf.ac.uk/id/eprint/58158

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