Meta-analysis and association of two common polymorphisms of the human oxytocin receptor gene in autism spectrum disorder

Autism Res. 2016 Oct;9(10):1036-1045. doi: 10.1002/aur.1597. Epub 2016 Jan 20.


Neuropeptides such as oxytocin (OXT) are known facilitators of social behavior across species. Variants of the OXT receptor gene (OXTR) have been tested for association with autism spectrum disorder (ASD) across manifold ethnicities, yielding both positive and negative findings. A recent meta-analysis, comprising 16 single nucleotide polymorphisms (SNPs), has corroborated the implication of OXTR in the etiology of ASD. Here, we genotyped and tested two additional variants (rs237889 and rs237897) for association with ASD in two German predominantly high-functioning ASD samples. We found nominal over-transmission (OR = 1.48, CI95 = 1.06-2.08, P = 0.022) for the minor A allele of variant rs237889G>A in sample 1 (N = 135 complete parent-offspring trios, 29 parent child duos), but not in sample 2 (362 trios, 69 duos). Still, in a meta-analysis comprising four different studies including the two unreported German data sets (N = 542 families), this finding was confirmed (OR = 1.12; CI95 = 1.01-1.24, random effects P = 0.012). In addition, carriers of the minor risk allele rs237889-A showed significantly increased severity scores, as assessed through the autism diagnostic interview - revised (ADI-R), with highly significant increases in social interaction deficits. Our results corroborate the implication of common OXTR variants in the etiology of ASD. There is a need for functional studies to delineate the neurobiological implications of this and other association findings. (172/250). Autism Res 2016, 9: 1036-1045. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

Keywords: autism spectrum disorder; endophenotype; genetics; genotyping; meta-analysis; oxytocin; oxytocin receptor; social interaction.

Publication types

  • Meta-Analysis

MeSH terms

  • Alleles
  • Autism Spectrum Disorder / genetics*
  • Child
  • Genotype
  • Humans
  • Polymorphism, Single Nucleotide / genetics*
  • Receptors, Oxytocin / genetics*


  • OXTR protein, human
  • Receptors, Oxytocin