Oxytocin Receptor (OXTR) Gene Polymorphism Contributes to Ability in Face Recognition Memory

Background: The ability to visually identify individuals, accomplished by facial recognition, is essential for successful social interactions. In autism, this ability is impaired. Social recognition abilities such as face recognition memory are heritable, thus by implication are influenced by genetic polymorphisms.  On the basis of animal studies, the oxytocin receptor (OXTR) gene plays a critical role in conspecific recognition memory.  We hypothesized that polymorphisms in this gene could contribute to variability in social recognition in humans.

Objectives: Our aim was to investigate the association between specific OXTR variants and face recognition memory, in children with autism and their family members. We selected this sample because our previous work had shown it was enriched for face recognition memory impairment, compared with typical population controls.

Methods: 661 participants from 194 families were recruited including 198 probands with autism (mean age=11.3±3.4 years; Full Scale IQ=97.6±17.8; male/female ratio=4.5:1), their parents and siblings. Autistic traits were measured using the Developmental, Dimensional and Diagnostic Interview (3Di) and the Autism Diagnostic Observation Schedule (ADOS). An age and sex-standardized score was obtained for all subjects (6-60 years of age) from the Warrington Face Recognition Memory Test. Saliva, buccal cell or blood samples were collected from the participants for DNA extraction. 59 SNPs from the OXTR gene were genotyped using a Sequenom platform. Genetic associations were analysed using QFAM-PLINK for quantitative familial traits, implemented in BC-Gene. p-ACT was used to correct for multiple comparisons.

Results:  We found SNP rs237887 is significantly associated with the face recognition memory endophenotype (p=0.0001522; corrected, p-ACT=0.023). The ancestral A allele of this SNP is associated with relatively impaired recognition memory in all family members. No transmission distortion was found in inheritance of this allele by probands. rs237887 is an intronic SNP located in a region that is predicted to interact with several transcription factors, suggesting a possible functional effect on OXTR gene expression.

Conclusions: This study implies evolutionary conservation of the role played by OXTR in social recognition memory, between animals (such as mice and voles) and humans. Our methodology emphasises the value of using age and sex-standardized endophenotypes to study genetic influences on cognitive traits relevant to ASD.