The Ludmer Centre for Neuroinformatics and Mental Health, Douglas Hospital Research Centre and Sackler Program for Epigenetics and Psychobiology, McGill University, Montreal, QC, H4H1R3, Canada.
Canadian Institute For Advanced Research, Child and Brain Development Program, Toronto, M5G 1Z8, Canada.
Transl Psychiatry. 2018 Jan 10;8(1):15. doi: 10.1038/s41398-017-0063-9.
This study reveals the influence of child maltreatment on DNA methylation across the genome and provides the first evidence that a psychosocial intervention program, the Nurse Family Partnership (NFP), which targets mothers at risk for abusive parenting, associates with variation in the DNA methylome in adult offspring. The 188 participants were born to women randomly assigned to control (n = 99) or nurse-visited intervention groups (n = 89) and provided blood samples and a diagnostic interview at age 27 years. Interindividual variation in the blood DNA methylome was described using principal components (PC) scores derived from principal component analysis and showed that the NFP program (PC10: p = 0.029) and a history of abuse/neglect (PC1: p = 0.029, PC2: p = 0.009) significantly associated with DNA methylome variation at 27 years of age independent of gender, ancestry, cellular heterogeneity, and a polygenic risk index for major psychiatric disorders. The magnitude of the association between child maltreatment and DNA methylation was reduced when accounting for lifestyle factors, including smoking. These findings reflect the sustained impact of both childhood adversity as well as intervention programs that target such adversity on the epigenome but highlight the need for prospective longitudinal studies of DNA methylome variation in the context of early intervention programs.
这项研究揭示了儿童虐待对整个基因组 DNA 甲基化的影响,并提供了第一个证据,即针对有虐待父母风险的母亲的心理社会干预计划——护士家庭伙伴关系(NFP)与成年后代 DNA 甲基化组的变化有关。188 名参与者的母亲在随机分配到对照组(n=99)或接受护士访问的干预组(n=89)时生下了他们,并在 27 岁时提供了血液样本和诊断访谈。使用主成分分析(PCA)得出的主成分(PC)分数描述了血液 DNA 甲基化组的个体间变异,并表明 NFP 计划(PC10:p=0.029)和虐待/忽视史(PC1:p=0.029,PC2:p=0.009)与 27 岁时的 DNA 甲基化组变异显著相关,独立于性别、祖源、细胞异质性和主要精神障碍的多基因风险指数。在考虑到包括吸烟在内的生活方式因素后,儿童虐待与 DNA 甲基化之间的关联程度降低。这些发现反映了童年逆境以及针对这种逆境的干预计划对表观基因组的持续影响,但强调了需要在早期干预计划背景下对 DNA 甲基化组变异进行前瞻性纵向研究。