Genetic Pathway Analysis of Inattentive Disorder Symptoms: A GWAS Study Analysis

Inattentive disorders represent a significant public health concern with substantial heritability, yet the specific genetic pathways underlying these conditions remain inadequately characterized. This study aimed to identify and analyse genetic variants associated with inattentive disorder symptoms through genome-wide association studies (GWAS) and subsequent pathway enrichment analysis. GWAS data from previous studies on inattentive disorder symptoms were extracted and mapped to genes. Comprehensive enrichment analyses were conducted using multiple databases including Cell Marker, Gene Ontology, KEGG, HMDB Metabolites, miRTarBase, PPI Hub Proteins and Reactome Pathways to identify biological pathways significantly associated with candidate genes. Ten genes were identified as significantly associated with inattentive disorder symptoms, including NOS1, GUCY1A2, PTCH1, PTPRN2, SLCO3A1, IL16, SPATA13, ZMAT4, DNAJB6 and ZNF423. Pathway analyses revealed significant enrichment in nitric oxide signaling, calcium ion regulation, hedgehog signaling pathway and neuron-specific cellular components. The most statistically significant pathway was nitric oxide stimulation of guanylate cyclase (p=0.0002621, adjusted p=0.0115). This study identifies novel genetic pathways potentially involved in the pathophysiology of inattentive disorders, particularly highlighting the role of nitric oxide signaling and calcium ion regulation. These findings provide promising targets for further investigation and potential therapeutic interventions for inattentive disorders.