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

AI Article Synopsis

  • Oxytocin (OT) is a crucial neuropeptide linked to social behavior and motivation, and its effectiveness in treating autism spectrum disorder (ASD) has shown mixed results.
  • A study examined the relationship between genetic and epigenetic factors and OT levels in 290 ASD participants involved in an OT clinical trial.
  • The researchers found new genetic connections to OT levels, linked to known ASD risk genes, and significant associations between OT levels and genetic expression or epigenetic changes, potentially aiding future research on ASD and OT therapy.

Article Abstract

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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10023458PMC
http://dx.doi.org/10.1002/aur.2884DOI Listing

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