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Shared genetic influences between attention-deficit/hyperactivity disorder (ADHD) traits in children and clinical ADHD

Stergiakouli, E., Martin, Joanna, Hamshere, Marian L., Langley, Kate, Evans, D. M., St Pourcain, B., Timpson, N. J., Owen, Michael John, O'Donovan, Michael Conlon, Thapar, Anita and Davey Smith, G 2015. Shared genetic influences between attention-deficit/hyperactivity disorder (ADHD) traits in children and clinical ADHD. Journal of the American Academy of Child and Adolescent Psychiatry 54 (4) , pp. 322-327. 10.1016/j.jaac.2015.01.010

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Abstract

Objective Twin studies and genome-wide complex trait analysis (GCTA) are not in agreement regarding heritability estimates for behavioral traits in children from the general population. This has sparked a debate on the possible difference in genetic architecture between behavioral traits and psychiatric disorders. In this study, we test whether polygenic risk scores associated with variation in attention-deficit/hyperactivity disorder (ADHD) trait levels in children from the general population predict ADHD diagnostic status and severity in an independent clinical sample. Method Single nucleotide polymorphisms (SNPs) with p < .5 from a genome-wide association study of ADHD traits in 4,546 children (mean age, 7 years 7 months) from the Avon Longitudinal Study of Parents and Children (ALSPAC; general population sample) were selected to calculate polygenic risk scores in 508 children with an ADHD diagnosis (independent clinical sample) and 5,081 control participants. Polygenic scores were tested for association with case-control status and severity of disorder in the clinical sample. Results Increased polygenic score for ADHD traits predicted ADHD case-control status (odds ratio = 1.17 [95% CI = 1.08–1.28], p = .0003), higher ADHD symptom severity (β = 0.29 [95% CI = 0.04–0.54], p = 0.02), and symptom domain severity in the clinical sample. Conclusion This study highlights the relevance of additive genetic variance in ADHD, and provides evidence that shared genetic factors contribute to both behavioral traits in the general population and psychiatric disorders at least in the case of ADHD.

Item Type: Article
Date Type: Publication
Status: Published
Schools: MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Medicine
Neuroscience and Mental Health Research Institute (NMHRI)
Subjects: R Medicine > R Medicine (General)
Uncontrolled Keywords: attention-deficit/hyperactivity disorder (ADHD), polygenic risk scores, Avon Longitudinal Study of Parents and Children (ALSPAC), common variants, genetics
Publisher: Elsevier
ISSN: 0890-8567
Date of First Compliant Deposit: 30 March 2016
Date of Acceptance: 26 January 2015
Last Modified: 20 Jun 2019 20:03
URI: http://orca.cf.ac.uk/id/eprint/76976

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