Oxytocin receptor gene variations predict neural and behavioral response to oxytocin in autism

Oxytocin appears beneficial for autism spectrum disorder (ASD), and more than 20 single-nucleotide polymorphisms (SNPs) in oxytocin receptor (OXTR) are relevant to ASD. However, neither biological functions of OXTR SNPs in ASD nor critical OXTR SNPs that determine oxytocin's effects on ASD rema...

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Published in:Social cognitive and affective neuroscience 2017-03, Vol.12 (3), p.496-506
Main Authors: Watanabe, Takamitsu, Otowa, Takeshi, Abe, Osamu, Kuwabara, Hitoshi, Aoki, Yuta, Natsubori, Tatsunobu, Takao, Hidemasa, Kakiuchi, Chihiro, Kondo, Kenji, Ikeda, Masashi, Iwata, Nakao, Kasai, Kiyoto, Sasaki, Tsukasa, Yamasue, Hidenori
Format: Article
Language:English
Subjects:
Adolescent
Adult
Algorithms
Alleles
Autism Spectrum Disorder - genetics
Autism Spectrum Disorder - physiopathology
Genetic Variation - genetics
Genotype
Humans
Machine Learning
Male
Original
Oxytocin - physiology
Polymorphism, Single Nucleotide - genetics
Receptors, Oxytocin - genetics
Social Behavior
Young Adult
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Summary:Oxytocin appears beneficial for autism spectrum disorder (ASD), and more than 20 single-nucleotide polymorphisms (SNPs) in oxytocin receptor (OXTR) are relevant to ASD. However, neither biological functions of OXTR SNPs in ASD nor critical OXTR SNPs that determine oxytocin's effects on ASD remains known. Here, using a machine-learning algorithm that was designed to evaluate collective effects of multiple SNPs and automatically identify most informative SNPs, we examined relationships between 27 representative OXTR SNPs and six types of behavioral/neural response to oxytocin in ASD individuals. The oxytocin effects were extracted from our previous placebo-controlled within-participant clinical trial administering single-dose intranasal oxytocin to 38 high-functioning adult Japanese ASD males. Consequently, we identified six different SNP sets that could accurately predict the six different oxytocin efficacies, and confirmed the robustness of these SNP selections against variations of the datasets and analysis parameters. Moreover, major alleles of several prominent OXTR SNPs-including rs53576 and rs2254298-were found to have dissociable effects on the oxytocin efficacies. These findings suggest biological functions of the OXTR SNP variants on autistic oxytocin responses, and implied that clinical oxytocin efficacy may be genetically predicted before its actual administration, which would contribute to establishment of future precision medicines for ASD.
ISSN:1749-5016
1749-5024
DOI:10.1093/scan/nsw150