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Association between the oxytocin receptor (OXTR) gene and autism: relationship to Vineland Adaptive Behavior Scales and cognition
Abstract
Evidence both from animal and human studies suggests that common polymorphisms in the oxytocin receptor (OXTR) gene are likely candidates to confer risk for autism spectrum disorders (ASD). In lower mammals, oxytocin is important in a wide range of social behaviors, and recent human studies have shown that administration of oxytocin modulates behavior in both clinical and non-clinical groups. Additionally, two linkage studies and two recent association investigations also underscore a possible role for the OXTR gene in predisposing to ASD. We undertook a comprehensive study of all 18 tagged SNPs across the entire OXTR gene region identified using HapMap data and the Haploview algorithm. Altogether 152 subjects diagnosed with ASDs (that is, DSM IV autistic disorder or pervasive developmental disorder--NOS) from 133 families were genotyped (parents and affected siblings). Both individual SNPs and haplotypes were tested for association using family-based association tests as provided in the UNPHASED set of programs. Significant association with single SNPs and haplotypes (global P-values <0.05, following permutation test adjustment) were observed with ASD. Association was also observed with IQ and the Vineland Adaptive Behavior Scales (VABS). In particular, a five-locus haplotype block (rs237897-rs13316193-rs237889-rs2254298-rs2268494) was significantly associated with ASD (nominal global P=0.000019; adjusted global P=0.009) and a single haplotype (carried by 7% of the population) within that block showed highly significant association (P=0.00005). This is the third association study, in a third ethnic group, showing that SNPs and haplotypes in the OXTR gene confer risk for ASD. The current investigation also shows association with IQ and total VABS scores (as well as the communication, daily living skills and socialization subdomains), suggesting that this gene shapes both cognition and daily living skills that may cross diagnostic boundaries.
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“many of these genetic studies have found that polymorphisms in the human OXT receptor (OXTR) gene are significantly associated with an ASD diagnosis and/or predict the severity of ASD4–12.”
From Effect of age and autism spectrum disorder on oxytocin receptor density in the human basal forebrain and midbrain (2018) · cites this paper as [7]
In the citing paper
“and others have reported associations with endophenotypes of ASD (20, 82, 83), including structural variability in brain regions relevant to social cognition (80, 84).”
From Variation in the Oxytocin Receptor Gene Predicts Brain Region–Specific Expression and Social Attachment (2016) · cites this paper as [82]
In the citing paper
“In addition to their roles in enhancing social behaviors, the AVPR1a and oxytocin receptor (OXTR) genes have been shown by us [25], [26] and others [27]–[30] to contribute to autism spectrum disorders (ASD), a behavioral disorder characterized by deficits in social communication and bonding.”
From The oxytocin receptor (OXTR) contributes to prosocial fund allocations in the dictator game and the social value orientations task (2009) · cites this paper as [25]
In the citing paper
“Of particular interest is rs1042778, which is significant both in our prior autism study[25], the 1st sample for both Dictator and SVO and in the second independently recruited DG sample.”
From The oxytocin receptor (OXTR) contributes to prosocial fund allocations in the dictator game and the social value orientations task (2009) · cites this paper as [25]
In the citing paper
“Notably, three of the SNPs (rs2268490, rs237887 and rs1042778) associated most robustly with the two economic decision tasks reported in the current investigation were also significantly associated with ASD[25].”
From The oxytocin receptor (OXTR) contributes to prosocial fund allocations in the dictator game and the social value orientations task (2009) · cites this paper as [25]
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Metadata
- Authors
- Lerer, E., Levi, S., Salomon, S., Darvasi, A., Yirmiya, N., & Ebstein, R. P.
- Affiliations
- Hebrew University of Jerusalem (IL)
- Corresponding author
- Ebstein, R P
- ORCID
- Ebstein, R P
- Venue
- Molecular Psychiatry
- Published
- 2007-09-25
- Volume
- 13
- Issue
- 10
- Pages
- 980-988
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- OpenAlex
- W2027676008
- Cited by
- 349
- References
- 54
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 4 · 2023: 10 · 2022: 11 · 2021: 10 · 2020: 9 · 2019: 9 · 2018: 13 · 2017: 19 · 2016: 28 · 2015: 31 · 2014: 29 · 2013: 39 · 2012: 36
- FWCI
- 9.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- oxytocin receptor gene, oxytocin receptor, autism spectrum disorder, single nucleotide polymorphisms, haplotypes, genetic association, family-based association, IQ, adaptive behavior, Vineland Adaptive Behavior Scales, pervasive developmental disorders, autism risk genes
- MeSH terms
- Activities of Daily Living, Adaptation, Psychological, Adolescent, Adult, Autistic Disorder, Child, Child, Preschool, Female, Gene Frequency, Genotype, Humans, Infant, Intelligence, Male, Receptors, Oxytocin, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Young Adult
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