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.