Oxytocin Receptor Genetic and Epigenetic Variations: Association With Child Abuse and Adult Psychiatric Symptoms.
Oxytocin Receptor Genetic and Epigenetic Variations: Association With Child Abuse and Adult Psychiatric Symptoms.
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DOI：
10.1111/cdev.12493
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发表时间：
2016-01
影响因子：
4.6
通讯作者：
Smith AK
中科院分区：
文献类型：
--
作者：
Smearman EL;Almli LM;Conneely KN;Brody GH;Sales JM;Bradley B;Ressler KJ;Smith AK
儿童期的虐待会改变生物系统，增加成人精神病理的风险。表观遗传机制，即调节基因表达的DNA结构的改变，是这种风险的潜在机制。虽然滥用与某些基因的甲基化有关，特别是在应激反应系统中，但迄今为止还没有研究评估过催产素受体（OXTR）的滥用和甲基化。然而，研究支持OXTR在滥用与不良成人结局之间的联系中的作用，表明滥用可使具有特定OXTR基因型的人出现更大的精神症状风险。因此，我们的研究试图(1)评估表观遗传学在虐待和精神病理之间的联系中的作用；(2)通过探索OXTR基因型和DNA CpG甲基化之间的关系，开始整合遗传学和表观遗传学文献。对393名非裔美国成年人（年龄= 41±12.8）进行了18个OXTR CpG位点、44个snp、儿童虐待、成人抑郁和焦虑症状的数据评估。总体而言，68%的基因型与附近CpG位点的甲基化相关，其中一部分存活了多次测试校正。儿童虐待与两个CpG位点的高甲基化相关，但没有在纠正中幸存下来，也没有作为精神病理的中介。然而，滥用与CpG甲基化相互作用可以预测精神病理。这些发现提示了OXTR在理解早期环境对成人精神症状的影响方面的作用。
Childhood abuse can alter biological systems and increase risk for adult psychopathology. Epigenetic mechanisms, alterations in DNA structure that regulate the gene expression, are a potential mechanism underlying this risk. While abuse associates with methylation of certain genes, particularly those in the stress response system, no study to date has evaluated abuse and methylation of the oxytocin receptor (OXTR). However, studies support a role for OXTR in the link between abuse and adverse adult outcomes, showing that abuse can confer greater risk for psychiatric symptoms in those with specific OXTR genotypes. Our study therefore sought to (1) assess the role of epigenetics in the link between abuse and psychopathology and (2) to begin to integrate the genetic and epigenetic literature by exploring associations between OXTR genotypes and DNA CpG methylation. Data on 18 OXTR CpG sites, 44 SNPs, childhood abuse, and adult depression and anxiety symptoms were assessed in 393 African American adults (age = 41±12.8). Overall, 68% of genotypes associated with methylation of nearby CpG sites, with a subset surviving multiple test correction. Child abuse associated with higher methylation of two CpG sites yet did not survive correction or serve as a mediator of psychopathology. However, abuse interacted with CpG methylation to predict psychopathology. These findings suggest a role for OXTR in understanding the influence of early environments on adult psychiatric symptoms.