A neurodevelopmental molecular network for ADHD
background Attention deficit hyperactivity disorder (adhd) is a highly heritable neuropsychiatric disorder. It is important to integrate the top findings of genome-wide association (gwa) studies, linkage studies, candidate gene studies, expression studies and animal models, and synthesise this information into molecular pathways that facilitate further research.
aim In this study, we investigated the presence of genomic convergence in the top findings of the five published genome-wide association studies (gwas) of adhd using various bioinformatics tools.
method We carried out bioinformatics pathway analyses using the Ingenuity and Biological Network Gene Ontology (Bingo) tool as well as a systematic literature analysis of 85 genes from the five published gwas containing single nucleotide polymorphisms (snps) associated with adhd at a P value < 1.00E-04.
results We found that 45 of the 85 topranked 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 aetiology. Several network proteins are also directly modulated by stimulants, the most commonly used psychopharmacological treatment for adhd.
conclusion We have identified a protein network for adhd that contributes to our understanding of the molecular basis of the disorder. In addition, our data suggest new candidate genes for adhd and provide clues to future research into psychopharmacological adhd treatments.