Exploring the molecular mechanisms of comorbidity between autism spectrum disorder and sleep disturbances through multi-dataset integration

Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder characterized by social interaction impairments and repetitive behaviors, often accompanied by sleep disturbances (SD). Despite extensive research, the molecular mechanisms underlying the co-occurrence of ASD and SD remain unclear. This study integrated gene expression data from the GEO database for ASD and SD. We performed differential gene expression analysis, functional enrichment analysis, and weighted gene co-expression network analysis (WGCNA) to identify key genes and pathways associated with both conditions. Additionally, we explored the potential regulatory roles of microRNAs (miRNAs) and transcription factors, and evaluated the therapeutic potential of drug repositioning using the CMap database. We identified LAMC3 as a common key gene in both ASD and SD, which plays a crucial role in neural development and is associated with cortical malformations. Functional enrichment analysis revealed significant associations with processes like oxidative stress, neurodevelopment, and immune responses. The miRNA-LAMC3 regulatory network highlighted several potential miRNAs, including hsa-miR-140-3p.1, which showed strong regulatory effects on LAMC3 expression. Immune infiltration analysis indicated significant differences in immune cell proportions between ASD and control groups, with LAMC3 positively correlated with certain immune cells. Our findings provide insights into the molecular links between ASD and SD, emphasizing the role of LAMC3 and its potential as a therapeutic target. The identified miRNAs and transcription factors offer new avenues for understanding the pathophysiology of these conditions. Further experimental validation and clinical trials are warranted to explore the therapeutic potential of identified compounds and to develop effective interventions for ASD and SD.