| Abstract |
Background: It is believed that the genetic cause of complex diseases, such as anxiety, is linked to a large genetic network. In recent years, there has been an increased number of studies reporting hundreds of genes associated with anxiety, posing the necessity of systematically study of the genetic network underlying the disease.Method: Anxiety-Gene relation data were extracted from the ResNet 11 Mammalian database, containing 592 anxiety candidate genes (nodes). Pathway enrichment analysis, Sub-Network Enrichment Analysis, Network Connectivity Analysis and Network Metrics Analysis were conducted to study network attributes and select the top nodes (genes). Additionally, Anxiety-Drug and Drug-Gene relation data were employed to study the Anxiety-Gene relation at the small molecule level. Results: 526 out of 592 genes enriched 100 anxiety candidate pathways (p<1e-15), demonstrating strong gene-gene interactions. Metrics analysis revealed 6 genes, DRD2, ADORA2A, IL1B, CRH, AVP, CRHR1, as top candidates for anxiety, in terms of replication frequency, network centrality and functional diversity. Additionally, the majority of the anxiety candidate genes (538/592) demonstrated strong interaction with 548/618 anxiety effective drugs, supporting the identified anxiety-gene relationship.Conclusion: Our results suggested that the genetic causes of anxiety were linked to a genetic network composed of a large group of genes. The gene network, together with the literature and enrichment metrics provided in this study, laid the groundwork for further biological/genetic studies in the field.
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