Translating Discoveries in Attention-Deficit/Hyperactivity Disorder Genomics to an Outpatient Child and Adolescent Psychiatric Cohort - 28/07/20
Abstract |
Objective |
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.
Method |
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.
Results |
Among referred youth, ADHD PRSs were associated with ADHD diagnoses, cross-diagnostic ADHD symptoms and academic impairment (odds ratios ∼1.4; R2 values ∼2%–3%), as well as cross-diagnostic variation in aggression and working memory. In adults, ADHD PRSs were 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 youth with a low burden (β coefficients ∼.2).
Conclusion |
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.
Le texte complet de cet article est disponible en PDF.Key words : ADHD, clinical translation, genomic medicine, polygenic risk
Plan
| Drs. Vuijk and Martin are co-first authors of this article. |
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| This research was supported by funding from the Stanley Center for Psychiatric Research and the National Institutes of Health (NIH) Grant No. R03MH106862 (to Dr. Doyle) and funding from the David Judah Foundation (to Drs. Doyle and Braaten). Dr. Martin was supported by the Wellcome Trust (Grant No. 106047). |
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| Drs. Vuijk and Martin served as the statistical experts for this research. |
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| Disclosure: Dr. Braaten has served on the boards of Magination Press and Beyond Booksmart. She has received royalties from books published by Guilford Press (Bright Kids Who Can’t Keep Up and The Child Clinician’s Report Writing Handbook) and by Sage (The Sage Encyclopedia of Intellectual and Developmental Disorders). Dr. Smoller is an unpaid member of the Bipolar/Depression Research Community Advisory Panel of 23andMe, is a Tepper Family MGH Research Scholar, and is supported in part by a gift from the Demarest Lloyd, Jr. Foundation. Dr. Faraone has received income, potential income, travel expenses, continuing education support, and/or research support from Tris, Otsuka, Arbor, Ironshore, Shire, Akili Interactive Labs, Enzymotec, Sunovion, Supernus, and Genomind. With his institution, he has U.S. patent US20130217707A1 for the use of sodium/hydrogen exchange inhibitors in the treatment of attention-deficit/hyperactivity disorder. In previous years, he has received support from Shire, Ironshore, Neurovance, Alcobra, Rhodes, CogCubed, KemPharm, Enzymotec, Akili Interactive Labs, NeuroLifeSciences, Lundbeck/Takeda, Otsuka, McNeil, Janssen, Novartis, Pfizer, and Eli Lilly. He has received royalties from books published by Guilford Press (Straight Talk About Your Child’s Mental Health), Oxford University Press (Schizophrenia: The Facts), and Elsevier (ADHD: Non-Pharmacologic Interventions). He is principal investigator of www.adhdinadults.com. He has also received direct support from the European Union’s Seventh Framework Programme for research, technological development, and demonstration under Grant Agreement No. 602805, the European Union’s Horizon 2020 research and innovation program under Grant Agreement Nos. 667302 and 728018, and National Institute of Mental Health (NIMH) Grant Nos. 5R01MH101519 and U01 MH109536-01. Dr. Perlis has held equity in Psy Therapeutics and Outermost Therapeutics, has served on the scientific advisory board of Genomind, and has served as a consultant to RID Ventures. He has received research funding from NIMH, the National Heart, Lung, and Blood Institute, the National Human Genome Research Institute, and Telefonica Alfa. Drs. Vuijk, Martin, Genovese, Capawana, O’Keefe, and Doyle and Mss. Lee and Lind have reported no biomedical financial interests or potential conflicts of interest. |
Vol 59 - N° 8
P. 964-977 - août 2020 Retour au numéro
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