RCTAutism research : official journal of the International Society for Autism Research2023

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

Stephen K Siecinski, Stephanie N Giamberardino, Marina Spanos and 35 others

PMID 36609850

WHAT IT FOUND

No common genetic variant was clearly linked to plasma oxytocin levels in 175 children and adolescents with ASD, though several variants and pathways showed possible associations.

Key findings

01No common genetic variant was clearly linked to plasma oxytocin, but fourteen variants showed possible links.

02Possible links included lower plasma oxytocin with RBFOX1 and higher with DLGAP2, TH, GNG2, CACNG3, PRKCB, GABBR1 and ADCY2.

03OXTR methylation and individual DNA methylation markers were not associated with plasma oxytocin, but pathway-level methylation analyses found associations.

STILL TO COME

How it was doneWhat they found

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What it does not show

The analyses were underpowered for genome-wide tests, and the authors say the 290-person trial cohort was insufficient for detecting small or moderate effects. The suggestive genetic findings were often based on very few carriers, especially in participants of African or mixed ancestry, so they need replication. Peripheral blood measures may not reflect brain oxytocin, and plasma oxytocin has a half-life of less than an hour, so one baseline sample may not capture it. The analyses reported here were molecular associations with plasma oxytocin, not tests of oxytocin treatment effects or patient outcomes. ELISA-based oxytocin assays can produce inconsistent results and are sensitive to protocol changes.

Declared interests

The authors declared no conflicts of interest. Publication metadata lists NIH and non-U.S. government support.

The easy way to misread this

Do not use these plasma oxytocin genetic or pathway findings to decide oxytocin treatment or to assess a patient. The study was exploratory, underpowered, found no common variant reaching the strongest threshold, and did not test clinical outcomes.

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The study

Participants
175
Certainty of evidence
Moderate

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    Stephen K Siecinski, Stephanie N Giamberardino, Marina Spanos, et al. Genetic and epigenetic signatures associated with plasma oxytocin levels in children and adolescents with autism spectrum disorder. Autism research : official journal of the International Society for Autism Research. 2023.

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