TIGP (BIO)—In the "Loop": Examining the Role of Circular RNAs in Human Diseases

Abstract

Autism spectrum disorder (ASD) is a highly pervasive neurodevelopmental disorder, but the underlying reasons for its increasing prevalence in the last two decades are still unclear. Circular RNAs (circRNAs), a type of long noncoding RNAs that are abundant in neural tissues and involved in neuronal development, have emerged as potentially important regulators in ASD. To shed light on the molecular mechanisms and pathogenesis of ASD, we conducted a large-scale analysis integrating RNA-sequencing and genotype data from autistic brains and healthy controls. Our findings suggest that circRNAs play a role in ASD pathogenesis, potentially by regulating microRNA and ASD-associated gene expression. We further investigated the relationships between genetic variants and transcriptional expression changes in ASD, focusing on the expression quantitative trait loci of circRNAs (circQTLs) that regulate circRNAs and distant genes. Our statistical analyses revealed the propagation paths of circQTL-circRNA-Gene-ASD diagnosis, supporting the relevance of ASD risk genes to the autistic pathophysiology, and the replication analysis in schizophrenia samples also supports the utility of our framework and strategies. To conclude, our work provides a framework for studying cryptic regulatory mechanisms underlying neuropsychiatric diseases and provides a perspective of potential therapies for ASD by modifying the specific genetic variants of circRNAs using DNA/RNA editing for future investigation.

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