RESEARCH Open Access Genetic variation in the oxytocin receptor (OXTR) gene is associated with Asperger Syndrome Agnese Di Napoli 1* , Varun Warrier 1 , Simon Baron-Cohen 1,2* and Bhismadev Chakrabarti 1,3 Abstract Background: Autism Spectrum Conditions (ASC) are a group of neurodevelopmental conditions characterized by impairments in communication and social interaction, alongside unusually repetitive behaviors and narrow interests. ASC are highly heritable and have complex patterns of inheritance where multiple genes are involved, alongside environmental and epigenetic factors. Asperger Syndrome (AS) is a subgroup of these conditions, where there is no history of language or cognitive delay. Animal models suggest a role for oxytocin (OXT) and oxytocin receptor (OXTR) genes in social-emotional behaviors, and several studies indicate that the oxytocin/oxytocin receptor system is altered in individuals with ASC. Previous studies have reported associations between genetic variations in the OXTR gene and ASC. Methods: The present study tested for an association between nine single nucleotide polymorphisms (SNPs) in the OXTR gene and AS in 530 individuals of Caucasian origin, using SNP association test and haplotype analysis. Results: There was a significant association between rs2268493 in OXTR and AS. Multiple haplotypes that include this SNP (rs2268493-rs2254298, rs2268490-rs2268493-rs2254298, rs2268493-rs2254298-rs53576, rs237885-rs22684 90-rs2268493-rs2254298, rs2268490-rs2268493-rs2254298-rs53576) were also associated with AS. rs2268493 has been previously associated with ASC and putatively alters several transcription factor-binding sites and regulates chromatin states, either directly or through other variants in linkage disequilibrium (LD). Conclusions: This study reports a significant association of the sequence variant rs2268493 in the OXTR gene and associated haplotypes with AS. Keywords: Autism Spectrum Conditions (ASC), Asperger Syndrome (AS), Oxytocin receptor (OXTR), Haplotype analysis Background Autism Spectrum Conditions (ASC) are a group of neu- rodevelopmental conditions characterized by difficulties in social interaction and communication, alongside un- usually repetitive behaviors and narrow interests. Classic autism and Asperger Syndrome (AS) are two subgroups of ASC. They differ in that AS (unlike classic autism) has no history of language or cognitive delay [1]. The prevalence of ASC in the general population is around 1% [2], with a male:female sex ratio of 4:1 in classic aut- ism [3], increasing to as high as 9:1 in AS [4]. ASC are highly heritable, as indicated in three different twin stud- ies [5-7]. Despite the high heritability, they are charac- terized by complex patterns of inheritance where multiple genes, epigenetic and environmental factors are involved. Many loci have been implicated in the predis- position to these conditions [8-10], but only a few of these loci have been well-replicated. The oxytocin receptor (OXTR) gene encodes a mem- ber of the class I family of G protein-coupled receptors, which contains seven transmembrane domains. It occu- pies 17 Kb on chromosome 3p25 and includes four exons and three introns. It is mainly expressed in the mammalian reproductive system and brain (pre-limbic circuits, nucleus accumbens, thalamus and amygdala) [11-13]. Oxytocin receptor (OXTR) regulates the activ- ity of oxytocin (OXT), a neuropeptide implicated in * Correspondence: agnesedinapoli@outlook.com; sb205@cam.ac.uk 1 Autism Research Centre, Department of Psychiatry, University of Cambridge, Douglas House, 18B Trumpington Road, Cambridge CB2 8AH, UK 2 Cambridgeshire and Peterborough NHS Foundation Trust, CLASS Clinic, Cambridge, Elizabeth House, Fulbourn Hospital, Cambridge CB21 5EF, UK Full list of author information is available at the end of the article © 2014 Di Napoli et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Di Napoli et al. Molecular Autism 2014, 5:48 http://www.molecularautism.com/content/5/1/48