An investigation of child maltreatment and epigenetic mechanisms of mental and physical health risk.
An investigation of child maltreatment and epigenetic mechanisms of mental and physical health risk.
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DOI：
10.1017/s0954579416000869
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发表时间：
2016-11
影响因子：
3.3
通讯作者：
Toth SL
中科院分区：
文献类型：
--
作者：
Cicchetti D;Hetzel S;Rogosch FA;Handley ED;Toth SL
本研究对548名低收入学龄儿童（女性47.8%，黑人67.7%，M年龄=9.40岁）进行了全基因组差异甲基化分析，其中54.4%有儿童虐待史。在夏季研究营的背景下，通过唾液获得了DNA样本。使用GenomeStudio、甲基化模块和Illumina定制模型，差异甲基化分析显示，在受虐待儿童中，低甲基化位点（n=197个位点）和中等甲基化位点（n=730个位点）的甲基化程度较高，而高甲基化位点（n=907个位点）的甲基化程度较低。受虐待儿童和未受虐待儿童甲基化的平均差异为6.2%。还使用GenoGo MetaCore软件调查了已知疾病生物标志物的虐待相对风险。大量先前与心理健康、癌症、心血管系统和免疫功能相关的网络对象被确定，证明在受虐待和未受虐待的儿童中甲基化存在差异。我们还对ALDH2、ANKK1和NR3C1进行了位点特异性分析，结果强调了考虑性别和虐待发育时间的重要性。对于ALDH2，结果表明，与未受虐待的女孩相比，受虐待的女孩的甲基化水平明显较低，而受虐待的男孩的甲基化水平明显高于未受虐待的男孩。此外，与未受虐待的男孩相比，早期发病的未受虐待男孩的ALDH2甲基化明显更高。同样，与未受虐待的儿童相比，早期发病的非近期虐待儿童的ANKK1甲基化明显更高。通过控制各自基因的基因型变异，位点特异性结果没有改变。研究结果表明，受虐待儿童的不良身心健康结果风险增加与甲基化差异有关，并表明受虐待儿童之间的差异与虐待的发育时间和涉及心理健康功能的基因的性别有关。
In the present investigation, differential methylation analyses of the whole genome were conducted among a sample of 548 school-aged low-income children (47.8% female, 67.7% Black, M age=9.40 years), 54.4% of whom had a history of child maltreatment. In the context of a summer research camp, DNA samples via saliva were obtained. Using GenomeStudio, Methylation Module and the Illumina Custom Model, differential methylation analyses revealed a pattern of greater methylation at low methylation sites (n=197 sites) and medium methylation sites (n=730 sites) and less methylation at high methylation sites (n=907 sites) among maltreated children. The mean difference in methylation between the maltreated and nonmaltreated children was 6.2%. The relative risk of maltreatment with known disease biomarkers was also investigated using GenoGo MetaCore Software. A large number of network objects previously associated with mental health, cancer, cardiovascular systems, and immune functioning were identified evidencing differential methylation among maltreated and nonmaltreated children. Site-specific analyses were also conducted for ALDH2, ANKK1, and NR3C1 and results highlight the importance of considering gender and the developmental timing of maltreatment. For ALDH2, results indicated that maltreated girls evidenced significantly lower methylation compared to nonmaltreated girls, and maltreated boys evidenced significantly higher methylation compared to nonmaltreated boys. Moreover, early onset-not recently maltreated boys evidenced significantly higher methylation at ALDH2 compared to nonmaltreated boys. Similarly, children with early onset-non recent maltreatment evidenced significantly higher methylation compared to nonmaltreated children at ANKK1. The site-specific results were not altered by controlling for genotypic variation of respective genes. The findings demonstrate increased risk for adverse physical and mental health outcomes associated with differences in methylation in maltreated children and indicate differences among maltreated children related to developmental timing of maltreatment and gender in genes involved in mental health functioning.