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

被引:165
作者
Poelmans, Geert
Pauls, David L.
Buitelaar, Jan K.
Franke, Barbara
机构
[1] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6500 HB Nijmegen, Netherlands
[2] Radboud Univ Nijmegen, Med Ctr, Dept Cognit Neurosci, NL-6500 HB Nijmegen, Netherlands
[3] Radboud Univ Nijmegen, Med Ctr, Dept Psychiat, NL-6500 HB Nijmegen, Netherlands
[4] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, NL-6500 HB Nijmegen, Netherlands
[5] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Psychiat & Neurodev Genet Unit,Ctr Human Genet Re, Boston, MA USA
关键词
DEFICIT/HYPERACTIVITY DISORDER; MOLECULAR-GENETICS; READING-DISABILITY; NEURITE OUTGROWTH; CANDIDATE GENE; ADULT ADHD; AMPHETAMINE; CHILDREN; METHYLPHENIDATE; METAANALYSIS;
D O I
10.1176/appi.ajp.2010.10070948
中图分类号
R749 [精神病学];
学科分类号
100205 ;
摘要
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.
引用
收藏
页码:365 / 377
页数:13
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