Evidence for the involvement of genetic variation in the oxytocin receptor gene (OXTR) in the etiology of autistic disorders on high-functioning level

Am J Med Genet B Neuropsychiatr Genet. 2010 Mar 5;153B(2):629-639. doi: 10.1002/ajmg.b.31032.


An increasing number of animal studies advert to a substantial role of the neuropeptide oxytocin in the regulation of social attachment and affiliation. Furthermore, animal studies showed anxiety and stress-reduced effects of oxytocin. First human studies confirm these findings in animal studies and implicate a crucial role of oxytocin in human social attachment behavior and in social interactions. Thus, the oxytocin system might be involved in the impairment of social interaction and attachment in autism spectrum disorders (ASD). The human oxytocin receptor gene (OXTR) represents a plausible candidate gene for the etiology of ASD. To analyze whether genetic variants in the OXTR gene are associated with ASD we performed family-based single-marker and haplotype association analyses with 22 single nucleotide polymorphisms (SNPs) in the OXTR and its 5' region in 100 families with autistic disorders on high-functioning level (Asperger syndrome (AS), high-functioning autism (HFA), and atypical autism (AA)). Single-marker and haplotype association analyses revealed nominally significant associations of one single SNP and one haplotype with autism, respectively. Furthermore, employing a "reverse phenotyping" approach, patients carrying the haplotype associated with autism showed nominally significant impairments in comparison to noncarriers of the haplotype in items of the Autism Diagnostic Interview-Revised algorithm describing aspects of social interaction and communication. In conclusion, our results implicate that genetic variation in the OXTR gene might be relevant in the etiology of autism on high-functioning level.

MeSH terms

  • Adolescent
  • Adult
  • Asperger Syndrome / genetics*
  • Autistic Disorder / diagnosis*
  • Autistic Disorder / genetics*
  • Child
  • Female
  • Genetic Markers
  • Genetic Variation*
  • Genotype
  • Humans
  • Linkage Disequilibrium*
  • Male
  • Models, Genetic
  • Polymorphism, Single Nucleotide*
  • Receptors, Oxytocin / genetics*


  • Genetic Markers
  • Receptors, Oxytocin