A common variant in OXTR rs53576 impacts topological patterns of brain functional networks


A common variant (rs53576, G/A) in the oxytocin receptor (OXTR) gene is associated with individual differences in social behavior and may increase the risk for neuropsychiatric disorders characterized by social impairment, especially autism. Although recent functional magnetic resonance imaging (fMRI) studies have identified functional connectivity alteration in some brain regions in risk A allele carriers, it is currently unknown whether this dysfunctional connectivity causes disruption of the topological properties of brain functional networks. We applied a graph-theoretical analysis to investigate the topological properties of brain networks derived from resting-state fMRI in relation to AA homozygotes versus G allele carriers in 290 cognitive normal young adults. We found both AA homozygotes and G allele carriers demonstrated small-world properties; however, male AA homozygotes showed lower normalized clustering coefficient, small-worldness, and local efficiency compared with male G allele carriers, no differences survived after Bonferroni correction; and the inter-group differences of all three metrics exhibited an allele-load-dependent trend (AA < AG < GG), indicating a randomization shift of their brain functional networks. No significant results were observed in any global measures in female AA homozygotes as compared to female G allele carriers. Our results suggested that the topological patterns of brain functional networks were altered in OXTR rs53576 male homozygotes for the risk A allele compared with male G allele carriers, providing evidence for the disruption of integrity in large-scale intrinsic brain networks in a sex-dimorphic manner.

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This work was supported by the Natural Science Foundation of China (Grant nos. 81871431, 81301201 and 81271551), the Natural Science Foundation of Tianjin Municipal Science and Technology Commission (Grant Nos. 18JCYBJC26300 and 18JCQNJC10900) and 2017 "New Century" Talent Training Project of Tianjin Medical University General Hospital.

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Guarantors of integrity of the entire study: JW and FL; study concepts/study design or data acquisition or data analysis/ interpretation: all authors; manuscript drafting for important intellectual content: all authors; approval of final version of submitted manuscript: all authors; literature research, JW, YZ, ZY, DZ, FL, and WQ; clinical studies, JZ and BL; experimental studies, WQ, JZ, and BL; statistical analysis, JW, YZ, ZY, DZ, FL, and WQ.

Corresponding authors

Correspondence to Junping Wang or Feng Liu.

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All the authors declare that they have no competing interests.

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All procedures performed in our studies involving 324 healthy young adults were in accordance with the ethical standards of Tianjin Medical University General Hospital and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. After a complete description of our study, written informed consent was obtained from all participants.

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The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Wang, J., Zhang, Y., Zhu, D. et al. A common variant in OXTR rs53576 impacts topological patterns of brain functional networks. Eur Child Adolesc Psychiatry 29, 993–1002 (2020). https://doi.org/10.1007/s00787-019-01414-5

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  • Oxytocin receptor gene
  • Resting-state functional magnetic resonance imaging
  • Small-world network
  • Graph-theoretical analysis