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Association between the oxytocin receptor (OXTR) gene and autism: relationship to Vineland Adaptive Behavior Scales and cognition

Molecular Psychiatry volume 13, pages 980–988 (2008)Cite this article

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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Acknowledgements

This research was partially supported by the Israel Science Foundation founded by the Israel Academy of Sciences and Humanities (NY and RPE).

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Authors and Affiliations

  1. Department of Human Genetics, Hebrew University, Jerusalem, Israel

    E Lerer

  2. Department of Child Psychiatry, Hadassah-Hebrew University Medical School, Jerusalem, Israel

    S Levi & R P Ebstein

  3. Department of Psychology, Hebrew University, Jerusalem, Israel

    S Salomon & N Yirmiya

  4. Faculty of Mathematics, The Alexander Silberman Institute of Life Sciences, Faculty of Science, Hebrew University, Jerusalem, Israel

    A Darvasi

  5. S Herzog Memorial Hospital, Jerusalem, Israel

    R P Ebstein

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Correspondence to R P Ebstein.

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All the authors contributed equally to the design, execution and preparation of this manuscript for publication.

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Lerer, E., Levi, S., Salomon, S. et al. Association between the oxytocin receptor (OXTR) gene and autism: relationship to Vineland Adaptive Behavior Scales and cognition. Mol Psychiatry 13, 980–988 (2008). https://doi.org/10.1038/sj.mp.4002087

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