Genetic and epigenetic signatures associated with plasma oxytocin levels in children and adolescents with autism spectrum disorder.

Scientists studied blood oxytocin levels in 290 children and teens with autism who were part of an oxytocin treatment study. They looked at genes and how genes are switched on/off to understand why some people have different oxytocin levels. They found specific genetic differences linked to oxytocin levels, including some in genes already known to be connected to autism. This research helps explain why oxytocin treatments work differently for different people with autism.

This study examined genetic and epigenetic factors that influence oxytocin levels in 290 children and adolescents with autism spectrum disorder enrolled in an oxytocin therapy trial. Researchers integrated genome-wide DNA methylation, gene expression, and genetic variation data with plasma oxytocin measurements. The analysis identified novel genetic variants associated with plasma oxytocin levels, including variants in known ASD risk genes. Additionally, statistically significant associations were found between plasma oxytocin levels and peripheral gene expression and DNA methylation patterns across multiple gene pathways.

These findings enhance understanding of the peripheral oxytocin system and provide genetic candidates for future research into ASD's complex etiology and oxytocin-based interventions.

Findings suggest genetic and epigenetic testing could potentially identify individuals most likely to benefit from oxytocin therapy. This research provides foundation for developing personalized approaches to oxytocin treatment in autism, though clinical validation is needed before implementation.

Abstract does not specify methodological details, effect sizes, or control comparisons. The clinical significance of identified associations remains unclear. Generalizability beyond the study population is unknown.

Oxytocin (OT), the brain's most abundant neuropeptide, plays an important role in social salience and motivation. Clinical trials of the efficacy of OT in autism spectrum disorder (ASD) have reported mixed results due in part to ASD's complex etiology. We investigated whether genetic and epigenetic variation contribute to variable endogenous OT levels that modulate sensitivity to OT therapy. To carry out this analysis, we integrated genome-wide profiles of DNA-methylation, transcriptional activity, and genetic variation with plasma OT levels in 290 participants with ASD enrolled in a randomized controlled trial of OT.

Our analysis identified genetic variants with novel association with plasma OT, several of which reside in known ASD risk genes. We also show subtle but statistically significant association of plasma OT levels with peripheral transcriptional activity and DNA-methylation profiles across several annotated gene sets. These findings broaden our understanding of the effects of the peripheral oxytocin system and provide novel genetic candidates for future studies to decode the complex etiology of ASD and its interaction with OT signaling and OT-based interventions. LAY SUMMARY: Oxytocin (OT) is an abundant chemical produced by neurons that plays an important role in social interaction and motivation.

We investigated whether genetic and epigenetic factors contribute to variable OT levels in the blood. To this, we integrated genetic, gene expression, and non-DNA regulated (epigenetic) signatures with blood OT levels in 290 participants with autism enrolled in an OT clinical trial. We identified genetic association with plasma OT, several of which reside in known autism risk genes. We also show statistically significant association of plasma OT levels with gene expression and epigenetic across several gene pathways.

These findings broaden our understanding of the factors that influence OT levels in the blood for future studies to decode the complex presentation of autism and its interaction with OT and OT-based treatment.