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Published Online: 1 April 2011

Integrated Genome-Wide Association Study Findings: Identification of a Neurodevelopmental Network for Attention Deficit Hyperactivity Disorder

Abstract

Objective:

Attention deficit hyperactivity disorder (ADHD) is a highly heritable neuropsychiatric disorder. In the present study, the authors investigated the presence of genomic convergence in the top findings of the five published genome-wide association studies (GWASs) of ADHD.

Method:

The authors carried out bioinformatics pathway analyses, using the Ingenuity and BiNGO tools, as well as a systematic literature analysis of 85 genes from the five published GWASs containing single nucleotide polymorphisms associated with ADHD at a p value <0.0001.

Results:

Findings revealed that 45 of the 85 top-ranked ADHD candidate genes encode proteins that fit into a neurodevelopmental network involved in directed neurite outgrowth. Data on copy number variations in patients with ADHD and data from animal studies provide further support for the involvement of this network in ADHD etiology. Several network proteins are also directly modulated by stimulants, the most commonly used psychopharmacological treatment for ADHD.

Conclusions:

The authors have identified a protein network for ADHD that contributes to our understanding of the molecular basis of the disorder. In addition, the data suggest new candidate genes for ADHD and provide clues to future research into psychopharmacological ADHD treatments.

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Information & Authors

Information

Published In

Go to American Journal of Psychiatry
Go to American Journal of Psychiatry
American Journal of Psychiatry
Pages: 365 - 377
PubMed: 21324949

History

Received: 6 July 2010
Revision received: 20 August 2010
Revision received: 19 October 2010
Accepted: 29 October 2010
Published online: 1 April 2011
Published in print: April 2011

Authors

Details

Geert Poelmans, M.D.
From the Department of Cognitive Neuroscience and Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, and the Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands; and the Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Harvard Medical School, Boston.
David L. Pauls, Ph.D.
From the Department of Cognitive Neuroscience and Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, and the Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands; and the Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Harvard Medical School, Boston.
Jan K. Buitelaar, M.D., Ph.D.
From the Department of Cognitive Neuroscience and Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, and the Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands; and the Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Harvard Medical School, Boston.
Barbara Franke, Ph.D.
From the Department of Cognitive Neuroscience and Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, and the Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands; and the Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Harvard Medical School, Boston.

Notes

Address correspondence and reprint requests to Dr. Franke, Department of Human Genetics (855), Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, the Netherlands; [email protected] (e-mail).

Funding Information

In the past 3 years, Dr. Buitelaar has been a consultant to, advisory board member of, and/or speaker for Bristol-Myers Squibb, Eli Lilly, Janssen-Cilag B.V., Medice, Organon/Shering Plough, Servier, Shire, and UCB. All other authors report no financial relationships with commercial interests.

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