Skip to main content
Journal cover image

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

Publication ,  Journal Article
Siecinski, SK; Giamberardino, SN; Spanos, M; Hauser, AC; Gibson, JR; Chandrasekhar, T; Trelles, MDP; Rockhill, CM; Palumbo, ML; Cundiff, AW ...
Published in: Autism Res
March 2023

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.

Duke Scholars

Published In

Autism Res

DOI

EISSN

1939-3806

Publication Date

March 2023

Volume

16

Issue

3

Start / End Page

502 / 523

Location

United States

Related Subject Headings

  • Oxytocin
  • Humans
  • Epigenesis, Genetic
  • Developmental & Child Psychology
  • DNA Methylation
  • Child
  • Autistic Disorder
  • Autism Spectrum Disorder
  • Adolescent
  • 5203 Clinical and health psychology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Siecinski, S. K., Giamberardino, S. N., Spanos, M., Hauser, A. C., Gibson, J. R., Chandrasekhar, T., … Gregory, S. G. (2023). Genetic and epigenetic signatures associated with plasma oxytocin levels in children and adolescents with autism spectrum disorder. Autism Res, 16(3), 502–523. https://doi.org/10.1002/aur.2884
Journal cover image

Published In

Autism Res

DOI

EISSN

1939-3806

Publication Date

March 2023

Volume

16

Issue

3

Start / End Page

502 / 523

Location

United States

Related Subject Headings

  • Oxytocin
  • Humans
  • Epigenesis, Genetic
  • Developmental & Child Psychology
  • DNA Methylation
  • Child
  • Autistic Disorder
  • Autism Spectrum Disorder
  • Adolescent
  • 5203 Clinical and health psychology