TY - JOUR
T1 - Oxytocin receptor gene variations predict neural and behavioral response to oxytocin in autism
AU - Watanabe, Takamitsu
AU - Otowa, Takeshi
AU - Abe, Osamu
AU - Kuwabara, Hitoshi
AU - Aoki, Yuta
AU - Natsubori, Tatsunobu
AU - Takao, Hidemasa
AU - Kakiuchi, Chihiro
AU - Kondo, Kenji
AU - Ikeda, Masashi
AU - Iwata, Nakao
AU - Kasai, Kiyoto
AU - Sasaki, Tsukasa
AU - Yamasue, Hidenori
N1 - Publisher Copyright:
© The Author (2016). Published by Oxford University Press.
PY - 2017/3/1
Y1 - 2017/3/1
N2 - 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.
AB - 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.
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U2 - 10.1093/scan/nsw150
DO - 10.1093/scan/nsw150
M3 - Article
C2 - 27798253
AN - SCOPUS:85020555611
SN - 1749-5016
VL - 12
SP - 496
EP - 506
JO - Social Cognitive and Affective Neuroscience
JF - Social Cognitive and Affective Neuroscience
IS - 3
ER -