Associations between oxytocin-related genes and autistic-like traits
Open accessAbstract
Oxytocin has repeatedly been shown to influence human behavior in social contexts; also, a relationship between oxytocin and the pathophysiology of autism spectrum disorder (ASD) has been suggested. In the present study, we investigated single-nucleotide polymorphisms (SNPs) in the oxytocin gene (OXT) and the genes for single-minded 1 (SIM1), aryl hydrocarbon receptor nuclear translocator 2 (ARNT2) and cluster of differentiation 38 (CD38) in a population of 1771 children from the Child and Adolescent Twin Study in Sweden (CATSS). Statistical analyses were performed to investigate any association between SNPs and autistic-like traits (ALTs), measured through ASD scores in the Autism-Tics, ADHD and other Co-morbidities inventory. Firstly, we found a statistically significant association between the SIM1 SNP rs3734354 (Pro352Thr) and scores for language impairment (p = .0004), but due to low statistical power this should be interpreted cautiously. Furthermore, nominal associations were found between ASD scores and SNPs in OXT, ARNT2 and CD38. In summary, the present study lends support to the hypothesis that oxytocin and oxytocin neuron development may have an influence on the development of ALTs and suggests a new candidate gene in the search for the pathophysiology of ASD.
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Evidence supporting a role for the genes encoding OXT and OXTR in ASD has been controversial.
“evidence supporting a role for the genes encoding OT (OXT) and the OT receptor (OXTR) has been more controversial (Allen-Brady et al., 2009; Ebstein et al., 2009; Hovey et al., 2014; Satterstrom et al., 2020; Willsey et al., 2013; Zhang et al., 2017)”
From Parallel social information processing circuits are differentially impacted in autism (2020) · cites this paper as Hovey et al., 2014
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“CD38 is implicated in the oxytocin signaling pathway, and single nucleotide polymorphisms in this gene have been associated with low serum oxytocin levels in autism spectrum disorder (ASD) patients [19, 34, 35].”
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Wilczyński, K. M., Zasada, I., Siwiec, A., & Janas-Kozik, M. H. (2019) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s207580 · Cited by 26 · see citing works
“Studies on uniovular twins revealed the presence of ASD in both siblings in 70–90% of the cases.(6,7) In around 10% of the cases, the ASD phenotype is secondary to other well-known diseases, such as fragile X syndrome, tuberous sclerosis complex, or metabolic disorders, e.”
BackgroundOlofsdotter, S., Åslund, C., Furmark, T., Comasco, E., & Nilsson, K. W. (2017) · Development and Psychopathology · doi:10.1017/s0954579417000967 · Cited by 24 · see citing works
Wilczyński, K. M., Siwiec, A., & Janas-Kozik, M. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00380 · Cited by 21 · see citing works
“Studies of uniovular twins have revealed the presence of ASD in both siblings in 70–90% of cases (7, 8).”
BackgroundGenetic variant rs17225178 in the ARNT2 gene is associated with Asperger Syndrome
Napoli, A. D., Warrier, V., Baron‐Cohen, S., & Chakrabarti, B. (2015) · Molecular Autism · doi:10.1186/s13229-015-0009-0 · Cited by 19 · see citing works
“Two previous studies have reported nominal association of rs3901896 with AS [27] and autistic traits (for example, language impairment) [28].”
InfluentialEmotion recognition associated with polymorphism in oxytocinergic pathway gene ARNT2
Hovey, D., Henningsson, S., Cortes, D. S., Bänziger, T., Zettergren, A., Melke, J., Fischer, H., Laukka, P., & Westberg, L. (2017) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nsx141 · Cited by 17 · see citing works
“Although there is as of yet no independent evidence of rs4778599 being functional, there is some previous evidence that this SNP and the intronic rs3901896 may be linked to autism spectrum diagnosis and autism traits (Chakrabarti et al., 2009; Hovey et al., 2014).”
BackgroundInfluentialMarazziti, D., Diep, P.-T., Carter, C. S., & Carbone, M. G. (2022) · Current Medicinal Chemistry · doi:10.2174/0929867329666220727120646 · Cited by 16 · see citing works
Towards Identifying Genetic Biomarkers for Gastrointestinal Dysfunction in Autism
Shindler, A. E., Hill‐Yardin, E. L., Petrovski, S., Bishop, N. E., & Franks, A. E. (2019) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-019-04231-6 · Cited by 12 · see citing works
Lupiañez, C. B., Martínez‐Bueno, M., Sánchez‐Maldonado, J. M., Badiola, J., Cunha, C., Springer, J., Lackner, M., Segura-Catena, J., Canet, L. M., Alcázar‐Fuoli, L., et al. (2020) · Infection and Immunity · doi:10.1128/iai.00882-19 · Cited by 12 · see citing works
“Although genetic studies have suggested that ARNT2 polymorphisms are involved in neurological diseases (43), little is known about their relationship with infectious diseases (44).”
BackgroundWade, M., Hoffmann, T. J., Knafo‐Noam, A., O’Connor, T. G., & Jenkins, J. M. (2016) · Hormones and Behavior · doi:10.1016/j.yhbeh.2016.05.002 · Cited by 8 · see citing works
“OXT rs2770378 has been linked to symptoms of autism, including language impairment and restrictive behavior (Hovey et al., 2014).”
Chong, A., Chew, S. H., Lai, P. S., Ebstein, R. P., & Gouin, J. (2018) · International Journal of Psychophysiology · doi:10.1016/j.ijpsycho.2018.02.015 · Cited by 8 · see citing works
Wilczyński, K. M., Auguściak-Duma, A., Stasik, A., Cichoń, L., Kawalec, A., & Janas-Kozik, M. H. (2023) · Current Issues in Molecular Biology · doi:10.3390/cimb45100527 · Cited by 5 · see citing works
“The Hovey et al. (2014) [22] study showed a link between the “C” allele of SNP rs6449182 in CD38 and the diagnosis of ASD, but the authors pointed to the inconclusivity of the results.”
ResultAngelopoulou, M., Siaperas, P., Livadas, S., Karantana, E., Papadimitriou, D. T., & Angelopoulos, N. (2025) · Neuroscience · doi:10.1016/j.neuroscience.2025.09.009 · Cited by 4 · see citing works
Oxytocin enhances creativity specifically in approach-motivated individuals
Yang, C., Guo, Z., & Cheng, L. (2025) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nsaf004 · Cited by 3 · see citing works
“…revealing positive correlations between OT-related genes and a spectrum of creativity-related traits, including imagination, cognitive flexibility, extraversion, and behavioral adaptability (Crespi and Sum-mers 2014, De Dreu et al. 2014, Haram et al. 2014, Hovey et al. 2014, De Dreu et al. 2015).”
Abdulamir, H. A., Al-Awadi, S. J. A., & Abdul‐Rasheed, O. F. (2016) · International Journal of Pharma and Bio Sciences
- Authors
- Hovey, D., Zettergren, A., Jonsson, L., Melke, J., Anckarsäter, H., Lichtenstein, P., & Westberg, L.
- Affiliations
- University of Gothenburg (SE)
- Karolinska Institutet (SE)
- Corresponding author
- Hovey, Daniel
- Venue
- Social Neuroscience
- Publisher
- Informa UK Limited
- Published
- 2014-03-17
- Volume
- 9
- Issue
- 4
- Pages
- 378-386
- ISSN
- 1747-0919 (ISSN-L)
- 1747-0927
- OpenAlex
- W2167059298
- Cited by
- 37
- References
- 60
- Citations by year
- 2025: 2 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 3 · 2019: 4 · 2018: 3 · 2017: 5 · 2016: 7 · 2015: 8 · 2014: 1
- FWCI
- 3.90
- Type
- journal article
- Language
- en
- Open access
- green
- figshare.com
- Licence
- cc-by-nc-nd
- Locations
- Social Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Figshare (submittedVersion, cc-by-nc-nd)
- Open Archive (Karolinska Institutet) (submittedVersion, cc-by-nc-nd)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- oxytocin, autism spectrum disorder, autistic traits, single nucleotide polymorphisms, SIM1, ARNT2, CD38, language impairment, genetic association, oxytocin neurons
- MeSH terms
- Child, Child Development Disorders, Pervasive, Female, Humans, Interviews as Topic, Language Development Disorders, Male, Membrane Glycoproteins, Oxytocin, Parents, Phenotype, Repressor Proteins, Social Behavior, Stereotyped Behavior, Sweden, Polymorphism, Single Nucleotide, Aryl Hydrocarbon Receptor Nuclear Translocator, Basic Helix-Loop-Helix Proteins, ADP-ribosyl Cyclase 1, Genotyping Techniques
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