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早年遭受重大逆境但童年后期未遭受此类逆境的青少年外周血单核细胞中的DNA甲基化差异。

Differential DNA methylation in peripheral blood mononuclear cells in adolescents exposed to significant early but not later childhood adversity.

作者信息

Esposito Elisa A, Jones Meaghan J, Doom Jenalee R, MacIsaac Julia L, Gunnar Megan R, Kobor Michael S

机构信息

University of Minnesota Institute of Child Development.

University of British Columbia Child and Family Research Institute.

出版信息

Dev Psychopathol. 2016 Nov;28(4pt2):1385-1399. doi: 10.1017/S0954579416000055. Epub 2016 Feb 5.

DOI:10.1017/S0954579416000055
PMID:26847422
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5903568/
Abstract

Internationally adopted adolescents who are adopted as young children from conditions of poverty and deprivation have poorer physical and mental health outcomes than do adolescents conceived, born, and raised in the United States by families similar to those who adopt internationally. Using a sample of Russian and Eastern European adoptees to control for Caucasian race and US birth, and nonadopted offspring of well-educated and well-resourced parents to control for postadoption conditions, we hypothesized that the important differences in environments, conception to adoption, might be reflected in epigenetic patterns between groups, specifically in DNA methylation. Thus, we conducted an epigenome-wide association study to compare DNA methylation profiles at approximately 416,000 individual CpG loci from peripheral blood mononuclear cells of 50 adopted youth and 33 nonadopted youth. Adopted youth averaged 22 months at adoption, and both groups averaged 15 years at testing; thus, roughly 80% of their lives were lived in similar circumstances. Although concurrent physical health did not differ, cell-type composition predicted using the DNA methylation data revealed a striking difference in the white blood cell-type composition of the adopted and nonadopted youth. After correcting for cell type and removing invariant probes, 30 CpG sites in 19 genes were more methylated in the adopted group. We also used an exploratory functional analysis that revealed that 223 gene ontology terms, clustered in neural and developmental categories, were significantly enriched between groups.

摘要

与在美国由类似国际收养家庭生育并抚养长大的青少年相比,那些在幼年时从贫困和匮乏环境中被国际收养的青少年身心健康状况较差。我们以俄罗斯和东欧被收养者为样本以控制白种人种族和美国出生因素,以受过良好教育且资源丰富的父母的非收养子女为样本以控制收养后的环境条件,我们假设从受孕到收养期间环境的重要差异可能反映在不同群体之间的表观遗传模式中,特别是在DNA甲基化方面。因此,我们进行了一项全表观基因组关联研究,比较了50名被收养青少年和33名非收养青少年外周血单核细胞中约416,000个个体CpG位点的DNA甲基化谱。被收养青少年平均在被收养时为22个月,两组在测试时平均年龄均为15岁;因此,他们大约80%的人生是在相似环境中度过的。虽然同时期的身体健康状况没有差异,但使用DNA甲基化数据预测的细胞类型组成显示,被收养青少年和非收养青少年的白细胞类型组成存在显著差异。在对细胞类型进行校正并去除不变探针后,19个基因中的30个CpG位点在被收养组中甲基化程度更高。我们还进行了一项探索性功能分析,结果显示,在神经和发育类别中聚类的223个基因本体术语在两组之间显著富集。

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