Network and pathway enrichment analysis of Attention Deficit/Hyperactivity Disorder candidate genes

Attention deficit/hyperactivity disorder (ADHD) is a well-known multigenic neurodevelopment disorder. It is a psychiatric disease which mainly affects the children and adolescence. Globally, 3%-5% of children are suffering from this mental disorder.

This disease is characterized by hyperactivity, impulsiveness and inattentiveness. Suffering individuals are also observed with sleep related problems. Though, its polygenic, to study the complexity of these genes, we used a purely network approach. Firstly, we collected all the candidate genes involved in ADHD through a literature survey.

We investigated these genes using STRING 10 and Cytoscape v 3.3.0 for protein protein interaction network. Accordingly, we attempted to identify the hub genes based on definite parameters like betweenness centrality, clustering coefficient and node degree using Network analyzer. Likewise, the key transcriptional regulators were acknowledged by means of MatInspector program. Finally, the enrichment analysis was executed using ClueGO.

As a result, dopamine receptor D2, brain derived neurotrophic factor, HTRF1A, and dopamine receptor D4 were recognized as hub genes among the reported ADHD genes. While, 17 transcription factors (TFs) were conveyed as the key TFs for these hub genes.

Functional enrichment analysis revealed regulation of dopamine and behavioral fear response pathways. These pathways have been assumed to play a central role in the ADHD within the selected candidate genes.