Translating Discoveries in Attention-Deficit/Hyperactivity Disorder Genomics to an Outpatient Child and Adolescent Psychiatric Cohort.
ADHD
clinical translation
genomic medicine
polygenic risk
Journal
Journal of the American Academy of Child and Adolescent Psychiatry
ISSN: 1527-5418
Titre abrégé: J Am Acad Child Adolesc Psychiatry
Pays: United States
ID NLM: 8704565
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
27
09
2018
revised:
29
05
2019
accepted:
08
08
2019
pubmed:
20
8
2019
medline:
19
3
2021
entrez:
18
8
2019
Statut:
ppublish
Résumé
Genomic discoveries should be investigated in generalizable child psychiatric samples in order 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 (PRSs) in relation to DSM-based ADHD phenotypes; 2) the association of ADHD PRSs with phenotypes beyond ADHD that share its liability and have implications for outcome; and 3) the extent to which youth with high ADHD PRSs manifest a distinctive clinical profile. Participants were 433 youth, ages 7-18 years, 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 genome-wide association study to date. We replicated key findings in 5,140 adult patients from a local health system biobank. Among referred youth, ADHD PRSs were associated with ADHD diagnoses, cross-diagnostic ADHD symptoms and academic impairment (odds ratios ∼1.4; R Among child and adolescent outpatients, ADHD polygenic risk was associated with ADHD and related phenotypes as well as clinical severity. These results extend the scientific foundation for studies of ADHD polygenic risk in the clinical setting and highlight directions for further research.
Identifiants
pubmed: 31421235
pii: S0890-8567(19)31455-8
doi: 10.1016/j.jaac.2019.08.004
pmc: PMC7408479
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
964-977Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : NIMH NIH HHS
ID : R01 MH101519
Pays : United States
Organisme : NIMH NIH HHS
ID : R03 MH106862
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH109536
Pays : United States
Organisme : Wellcome Trust
ID : 106047
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2019 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.
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