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社会经济变化可预测儿童全基因组 DNA 甲基化。

Socioeconomic changes predict genome-wide DNA methylation in childhood.

机构信息

Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.

Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.

出版信息

Hum Mol Genet. 2023 Feb 19;32(5):709-719. doi: 10.1093/hmg/ddac171.

Abstract

Childhood socioeconomic position (SEP) is a major determinant of health and well-being across the entire life course. To effectively prevent and reduce health risks related to SEP, it is critical to better understand when and under what circumstances socioeconomic adversity shapes biological processes. DNA methylation (DNAm) is one such mechanism for how early life adversity 'gets under the skin'. In this study, we evaluated the dynamic relationship between SEP and DNAm across childhood using data from 946 mother-child pairs in the Avon Longitudinal Study of Parents and Children. We assessed six SEP indicators spanning financial, occupational and residential domains during very early childhood (ages 0-2), early childhood (ages 3-5) and middle childhood (ages 6-7). Epigenome-wide DNAm was measured at 412 956 cytosine-guanines (CpGs) from peripheral blood at age 7. Using an innovative two-stage structured life-course modeling approach, we tested three life-course hypotheses for how SEP shapes DNAm profiles-accumulation, sensitive period and mobility. We showed that changes in the socioeconomic environment were associated with the greatest differences in DNAm, and that middle childhood may be a potential sensitive period when socioeconomic instability is especially important in shaping DNAm. Top SEP-related DNAm CpGs were overrepresented in genes involved in pathways important for neural development, immune function and metabolic processes. Our findings highlight the importance of socioeconomic stability during childhood and if replicated, may emphasize the need for public programs to help children and families experiencing socioeconomic instability and other forms of socioeconomic adversity.

摘要

儿童时期的社会经济地位(SEP)是整个生命周期中健康和幸福感的主要决定因素。为了有效预防和减少与 SEP 相关的健康风险,必须更好地了解社会经济逆境何时以及在何种情况下塑造生物过程。DNA 甲基化(DNAm)是早期逆境“影响皮肤”的一种机制。在这项研究中,我们使用了来自阿冯纵向研究父母和儿童的 946 对母婴数据,评估了 SEP 和 DNAm 在整个儿童期的动态关系。我们评估了六个涵盖金融、职业和居住领域的 SEP 指标,这些指标在儿童早期(0-2 岁)、幼儿期(3-5 岁)和儿童中期(6-7 岁)期间出现。在 7 岁时,通过外周血测量了 412956 个胞嘧啶-鸟嘌呤(CpG)的全基因组 DNAm。使用创新的两阶段结构化生命历程建模方法,我们检验了三种生命历程假设,即 SEP 如何塑造 DNAm 谱-积累、敏感时期和流动性。我们表明,社会经济环境的变化与 DNAm 差异最大相关,而儿童中期可能是一个潜在的敏感时期,社会经济不稳定在塑造 DNAm 方面尤为重要。与 SEP 相关的 DNAm CpG 在前额叶皮层中富集较多,这些 CpG 与神经发育、免疫功能和代谢过程相关基因有关。我们的研究结果强调了儿童时期社会经济稳定的重要性,如果得到证实,可能强调需要公共计划来帮助经历社会经济不稳定和其他形式社会经济逆境的儿童和家庭。

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