Epigenetic effects of early life on adult pathology

严重的童年逆境被认为是三大公共卫生问题的最大风险因素之一：心血管疾病、上呼吸道感染和精神健康问题。这三种疾病都与我们身体对压力的反应变化有关。主要的应激反应系统，下丘脑-垂体-肾上腺（HPA）轴，受到环境的制约，特别是在生命早期。环境和基因组之间的主要界面是基因组DNA的表观遗传甲基化。不良的早期生活经历与表观遗传DNA甲基化导致的HPA轴失调之间存在明显的联系。相关的病理，如心血管疾病和精神健康问题也与表观遗传改变有关。我们的工作假设是，早期生活中的逆境会导致上述疾病的高风险表观遗传修饰。我们认为，涉及上述所有三种疾病组的全基因组表观遗传修饰具有共同的早期生命起源。这将在一组年轻人中进行调查。预计该队列将继续用于EpiPath和其他药物的后续研究。可以预见的是，在未来的项目中，本项目中发现的表观遗传标记的预后和诊断价值将作为ELA的生物标志物和晚年病理的风险因素进行重新检查。

Severe childhood adversity is thought to be one of the strongest risk factors for three major public health problems: cardiovascular disease, upper respiratory tract infections (URTI) and mental health problems. The three disease groups have all been linked to changes in how our body responds to stress. The main stress response system, the hypothalamus-pituitary-adrenal (HPA) axis, is conditioned by the environment, particularly during early life.The principal interface between the environment and the genome is epigenetic methylation of genomic DNA. There is a clear link between adverse early life experiences and disregulation of the HPA axis by epigenetic DNA methylation. The associated pathologies such as cardiovascular diseases and mental health problems have also been associated with epigenetic alterations. Our working hypothesis is that early life adversity induces high risk epigenetic modifications for the above disorders. We suggest that genome wide epigenetic modifications, implicated in all three of the above disease groups, have a common early life origin. This will be investigated in a cohort of young adults. It is also envisaged that the cohort will be maintained for follow-up studies of EpiPath and others. It can be anticipated that in future projects the prognostic and diagnostic value of the epigenetic marks identified in this project will be reexamined both as biomarkers of ELA and as risk factors for later-life pathologies.