Association between oxytocin receptor gene polymorphisms and autistic traits as measured by the Autism-Spectrum Quotient in a non-clinical Japanese population

Introduction: Oxytocin is known to facilitate human behavior and social cognition related to autism. Subclinical autistic traits are continuously distributed in the general population. The aim of this study was to explore the association between oxytocin receptor gene (OXTR) polymorphisms and autistic traits. Methods: Participants consisted of 440 healthy Japanese (272 males and 168 females; mean age 40.9 +/- 9.7 years). Participants completed the Japanese version of the Autism-Spectrum Quotient (AQ) and donated a whole blood sample. Fifteen OXTR single nucleotide polymorphisms (SNPs) were genotyped using TaqMan or by direct sequencing. Single SNP linear regression analysis, permuted 10,000 times, and haplotype linear regression analysis, were conducted for the AQ and its subscale scores. Results: Three SNPs - rs2268490, rs2301261, and rs1042778 - were excluded from analysis, as the genotype distributions of rs2268490 were not in Hardy-Weinberg equilibrium, and there were less than 10 minor homozygous participants for rs2301261 and rs1042778. This resulted in 12 SNPs being tested. rs62243370, rs62243369, rs2254298, and rs2268491 were associated with attention switching subscale in females by the single SNP analysis. However, after performing Bonferroni corrections, statistical significances were eliminated. The attention switching subscale was associated with a specific haplotype, comprising rs62243370, rs62243369, rs13316193, rs2254298, rs2268493, and rs2268491 (GGTGTC, corrected P = 0.0016) in females. Discussion: The present study demonstrated a significant association between a specific OXTR haplotype and the autistic trait of "strong focus of attention" as measured by the AQ in a non-clinical female Japanese sample.