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Translating discoveries in Attention-Deficit/Hyperactivity Disorder genomics to an outpatient child and adolescent psychiatric cohort

Vuijk, Pieter J., Martin, Joanna ORCID:, Braaten, Ellen B., Genovese, Giulio, Capawana, Michael R., O'Keefe, Sheila M., Lee, B. Andi, Lind, Hannah S., Smoller, Jordan W., Faraone, Stephen V., Perlis, Roy H. and Doyle, Alysa E. 2020. Translating discoveries in Attention-Deficit/Hyperactivity Disorder genomics to an outpatient child and adolescent psychiatric cohort. Journal of the American Academy of Child and Adolescent Psychiatry 59 (8) , pp. 964-977. 10.1016/j.jaac.2019.08.004

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Objective Genomic discoveries should be investigated in generalizable child psychiatric samples to justify and inform studies that will evaluate their use for specific clinical purposes. In youth consecutively referred for neuropsychiatric evaluation, we examined: 1) the convergent and discriminant validity of attention-deficit/hyperactivity disorder (ADHD) polygenic risk scores (PRS) in relation to DSM-based ADHD phenotypes; 2) the association of ADHD PRS with phenotypes beyond ADHD that share its liability and have implications for outcome; and 3) the extent to which youth with high ADHD PRS manifest a distinctive clinical profile. Method Participants were 433 youth, ages 7 to 18, from the Longitudinal Study of Genetic Influences on Cognition. We used logistic/linear regression and mixed effects models to examine associations with ADHD-related polygenic variation from the largest ADHD GWAS to date. We replicated key findings in 5140 adult patients from a local health system biobank. Results Among referred youth, ADHD PRS associated with ADHD diagnoses, cross-diagnostic ADHD symptoms and academic impairment (OR’s ∼1.4; R2‘s ∼2-3%) as well as cross-diagnostic variation in aggression and working memory. In adults, ADHD PRS associated with ADHD and phenotypes beyond the condition that have public health implications. Finally, youth with a high ADHD polygenic burden showed a more severe clinical profile than those with low burden (beta’s∼.2). Conclusion Among child and adolescent outpatients, ADHD polygenic risk associated with ADHD and related phenotypes as well as clinical severity. Results extend the scientific foundation for studies of ADHD polygenic risk in the clinical setting and highlight directions for further research.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Publisher: Elsevier
ISSN: 0890-8567
Funders: Wellcome Trust
Date of First Compliant Deposit: 28 August 2019
Date of Acceptance: 8 August 2019
Last Modified: 06 May 2023 04:42

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