A common variant in OXTR rs53576 impacts topological patterns of brain functional networks
A common variant in OXTR rs53576 impacts topological patterns of brain functional networks
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DOI：
10.1007/s00787-019-01414-5
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发表时间：
2019-10
影响因子：
6.4
通讯作者：
Junping Wang;Yan Zhang;Dan Zhu;Zonghe Yang;Feng Liu;W. Qin;Jiajia Zhu;Bing Liu;T. Jiang;Chunshui Yu
中科院分区：
文献类型：
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作者：
Junping Wang;Yan Zhang;Dan Zhu;Zonghe Yang;Feng Liu;W. Qin;Jiajia Zhu;Bing Liu;T. Jiang;Chunshui Yu
催产素受体（OXTR）基因中的一种常见变体（rs 53576，G/A）与社会行为的个体差异相关，并可能增加以社会障碍为特征的神经精神疾病的风险，特别是自闭症。虽然最近的功能性磁共振成像（fMRI）研究已经确定了在风险A等位基因携带者的一些大脑区域的功能连接改变，目前尚不清楚这种功能障碍的连接是否会导致大脑功能网络的拓扑特性的破坏。我们应用图论分析，以调查来自静息态功能磁共振成像的大脑网络的拓扑特性，AA纯合子与G等位基因携带者在290个认知正常的年轻人。结果发现，AA纯合子和G等位基因携带者均表现出小世界特征，但男性AA纯合子的标准化聚类系数、小世界性和局部效率均低于男性G等位基因携带者，经Bonferroni校正后差异不显著;所有三个指标的组间差异均表现出等位基因负荷依赖的趋势（AA < AG < GG），表明他们的大脑功能网络的随机化移位。与女性G等位基因携带者相比，在女性AA纯合子的任何总体测量中均未观察到显著结果。我们的研究结果表明，与男性G等位基因携带者相比，OXTRrs 53576男性风险A等位基因纯合子的脑功能网络的拓扑模式发生了改变，为大规模内在脑网络的完整性以性别二态方式破坏提供了证据。
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 inOXTRrs53576 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.