Objective: Attention deficit hyperactivity disorder (ADHD) is a common, highly heritable neuropsychiatric disorder. ADHD often co-occurs with intellectual disability, and shared overlapping genetics have been suggested. The aim of this study was to identify novel ADHD genes by investigating whether genes carrying rare mutations linked to intellectual disability contribute to ADHD risk through common genetic variants. Validation and characterization of candidates were performed using Drosophila melanogaster.
Methods: Common genetic variants in a diagnostic gene panel of 396 autosomal intellectual disability genes were tested for association with ADHD risk through gene set and gene-wide analyses, using ADHD meta-analytic data from the Psychiatric Genomics Consortium for discovery (N=19,210) and ADHD data from the Lundbeck Foundation Initiative for Integrative Psychiatric Research for replication (N=37,076). The significant genes were functionally validated and characterized in Drosophila by assessing locomotor activity and sleep upon knockdown of those genes in brain circuits.
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The participant will describe the genetic architecture of attention deficit hyperactivity disorder (ADHD) and discover how the modeling of ADHD genetic effects in an alternative animal model system can contribute to the identification of biological pathways involved in ADHD.
This program is designed for all psychiatrists in clinical practice, residents in Graduate Medical Education programs, medical students interested in psychiatry, and other physicians who wish to advance their current knowledge of clinical medicine.
In order to earn CME credit, subscribers should read through the material presented in the article. After reading the article, complete the quiz and submit your evaluation and study hours (up to 1 AMA PRA Category 1 Credit™). A score of 60% or higher is required to receive credit.
The American Psychiatric Association (APA) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.
The APA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
Title: Contribution of Intellectual Disability–Related Genes to ADHD Risk and to Locomotor Activity in Drosophila
Authors: Marieke Klein, Ph.D., Euginia L. Singgih, B.Sc., Anne van Rens, M.Sc., Ditte Demontis, Ph.D., Anders D. Børglum, M.D., Ph.D., Nina Roth Mota, Ph.D., Anna Castells-Nobau, Ph.D., Lambertus A. Kiemeney, Ph.D., Han G. Brunner, M.D., Ph.D., Alejandro Arias-Vasquez, Ph.D., Annette Schenck, Ph.D., Monique van der Voet, Ph.D., Barbara Franke, Ph.D.
Affiliations: Department of Human Genetics (M.K., E.L.S., A.v.R., N.R.M., A.C.-N., H.G.B., A.A.-V., A.S., M.v.d.V., B.F.), Department of Psychiatry (N.R.M., A.A.-V., B.F.), and Department for Health Evidence (L.A.K.), Radboud University Medical Center and Donders Institute for Brain, Cognition, and Behavior, Nijmegen, the Netherlands; Department of Biomedicine and Center for Integrative Sequencing (iSEQ), Aarhus University, Aarhus, Denmark (D.D., A.D.B.); and Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Denmark (D.D., A.D.B.).
Disclosures: Dr. Børglum has received funding from the Lundbeck Foundation. Dr. Franke has received educational speaking fees from Shire and Medice. The other authors report no financial relationships with commercial interests.
Discussion of unapproved or investigational use of products*: No.
*APA policy requires disclosure by CME authors of unapproved or investigational use of products discussed in CME programs. Off-label use of medications by individual physicians is permitted and common. Decisions about off-label use can be guided by scientific literature and clinical experience.
Ned H. Kalin, M.D. (Editor-in-Chief, AJP); Carolyn Rodriguez, M.D., Ph.D. (Deputy Editor, AJP); Michael D. Roy (Editorial Director, AJP); Michael A. Pogachar (Online Content Manager, Journals). Dr. Kalin has served as a consultant to the Board of Scientific Advisors, the Pritzker Neuropsychiatric Disorders Research Consortium, and the Skyland Trail Advisory Board and as Councilor, Society of Biological Psychiatry. Dr. Rodriguez has served as a consultant to Allergan, Blackthorn, Epiodyne, and Rugen. Mr. Roy and Mr. Pogachar report no financial relationships with commercial interests.
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