Park Bongsoo, Khanam Rasheda, Vinayachandran Vinesh, Baqui Abdullah H, London Stephanie J, Biswal Shyam
Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
Department of International Health, Johns Hopkins Bloomberg School of Public Health, International Center for Maternal and Newborn Health, Baltimore, MD 21205, USA.
Environ Epigenet. 2020 Jun 14;6(1):dvaa005. doi: 10.1093/eep/dvaa005. eCollection 2020 Jan.
Preterm birth (PTB) is a major public health challenge, and novel, sensitive approaches to predict PTB are still evolving. Epigenomic markers are being explored as biomarkers of PTB because of their molecular stability compared to gene expression. This approach is also relatively new compared to gene-based diagnostics, which relies on mutations or single nucleotide polymorphisms. The fundamental principle of epigenome diagnostics is that epigenetic reprogramming in the target tissue (e.g. placental tissue) might be captured by more accessible surrogate tissue (e.g. blood) using biochemical epigenome assays on circulating DNA that incorporate methylation, histone modifications, nucleosome positioning, and/or chromatin accessibility. Epigenomic-based biomarkers may hold great potential for early identification of the majority of PTBs that are not associated with genetic variants or mutations. In this review, we discuss recent advances made in the development of epigenome assays focusing on its potential exploration for association and prediction of PTB. We also summarize population-level cohort studies conducted in the USA and globally that provide opportunities for genetic and epigenetic marker development for PTB. In addition, we summarize publicly available epigenome resources and published PTB studies. We particularly focus on ongoing genome-wide DNA methylation and epigenome-wide association studies. Finally, we review the limitations of current research, the importance of establishing a comprehensive biobank, and possible directions for future studies in identifying effective epigenome biomarkers to enhance health outcomes for pregnant women at risk of PTB and their infants.
早产是一项重大的公共卫生挑战，预测早产的新颖、敏感方法仍在不断发展。由于表观基因组标记与基因表达相比具有分子稳定性，因此正在探索将其作为早产的生物标志物。与基于基因的诊断方法相比，这种方法也相对较新，基于基因的诊断依赖于突变或单核苷酸多态性。表观基因组诊断的基本原理是，使用对循环DNA进行的生化表观基因组检测（包括甲基化、组蛋白修饰、核小体定位和/或染色质可及性），更易获取的替代组织（如血液）可能会捕获靶组织（如胎盘组织）中的表观遗传重编程。基于表观基因组的生物标志物在早期识别大多数与遗传变异或突变无关的早产方面可能具有巨大潜力。在本综述中，我们讨论了表观基因组检测开发方面的最新进展，重点关注其在早产关联和预测方面的潜在探索。我们还总结了在美国和全球范围内进行的人群水平队列研究，这些研究为早产的遗传和表观遗传标记开发提供了机会。此外，我们总结了公开可用的表观基因组资源和已发表的早产研究。我们特别关注正在进行的全基因组DNA甲基化和全表观基因组关联研究。最后，我们回顾了当前研究的局限性、建立综合生物样本库的重要性，以及未来研究在识别有效的表观基因组生物标志物以改善有早产风险的孕妇及其婴儿健康结局方面的可能方向。
