Autism spectrum disorder (ASD) is a genetic neurodevelopmental disorder involving multiple genes that occurs in early childhood, and a number of risk genes have been reported in previous studies. However, the molecular mechanism of the polygenic regulation leading to pathological changes in ASD remains unclear. First, we identified 8 dysregulated gene coexpression modules by analyzing blood transcriptome data from 96 children with ASD and 42 controls. These modules are rich in ASD risk genes and function related to metabolism, immunity, neurodevelopment, and signaling. The regulatory factors of each module including microRNA (miRNA) and transcription factors (TFs) were subsequently predicted based on transcriptional and posttranscriptional regulation. We identified a set of miRNAs that regulate metabolic and immune modules, as well as transcription factors that cause dysregulation of the modules, and we constructed a coregulatory network between the regulatory factors and modules. Our work reveals dysfunctional modules in children with ASD, elucidates the role of miRNA and transcription factor dysregulation in the pathophysiology of ASD, and helps us to further understand the underlying molecular mechanism of ASD.

自闭症谱系障碍 (ASD) 是一种遗传性神经发育障碍，涉及多个基因，发生在儿童早期，之前的研究中已经报道了许多风险基因。然而，导致 ASD 病理变化的多基因调控的分子机制尚不清楚。首先，我们通过分析来自 96 名 ASD 儿童和 42 名对照的血液转录组数据，确定了 8 个失调的基因共表达模块。这些模块富含 ASD 风险基因和与新陈代谢、免疫、神经发育和信号传导相关的功能。随后基于转录和转录后调控预测了每个模块的调控因子，包括 microRNA (miRNA) 和转录因子 (TFs)。我们确定了一组调节代谢和免疫模块的 miRNA，以及导致模块失调的转录因子，我们在调节因子和模块之间构建了一个协同调节网络。我们的工作揭示了 ASD 儿童的功能障碍模块，阐明了 miRNA 和转录因子失调在 ASD 病理生理学中的作用，并帮助我们进一步了解 ASD 的潜在分子机制。