Department of Epidemiology, Brown University, Providence, Rhode Island, USA.
Environ Mol Mutagen. 2013 Aug;54(7):533-41. doi: 10.1002/em.21762. Epub 2013 Feb 26.
Cost-effective, high-throughput epigenomic technologies have begun to emerge, rapidly replacing the candidate gene approach to molecular epidemiology and offering a comprehensive strategy for the study of epigenetics in human subjects. Epigenome-wide association studies (EWAS) provide new opportunities for advancing our understanding of epigenetic changes associated with complex disease states. However, such analyses are complicated by the dynamic nature of DNA methylation. In contrast to genomic studies, where genotype is essentially constant across somatic cells, EWAS present a new set of challenges, largely due to differential DNA methylation across distinct cell types, particularly for studies involving heterogeneous tissue sources, and changes in the epigenetic profile that occur over time. This review describes potential applications of EWAS from the viewpoint of the molecular epidemiologist, along with special considerations and pitfalls involved in the design of such studies.
成本效益高、高通量的表观基因组学技术开始出现,迅速取代了候选基因方法在分子流行病学中的应用,为人类表观遗传学研究提供了全面的策略。全基因组关联研究 (EWAS) 为我们深入了解与复杂疾病状态相关的表观遗传变化提供了新的机会。然而,这种分析受到 DNA 甲基化动态性质的影响。与基因组研究不同,基因型在体细胞中基本保持不变,EWAS 提出了一系列新的挑战,主要是由于不同细胞类型之间的 DNA 甲基化存在差异,特别是对于涉及异质组织来源的研究,以及随着时间的推移发生的表观遗传谱变化。本综述从分子流行病学家的角度描述了 EWAS 的潜在应用,以及此类研究设计中涉及的特殊考虑因素和陷阱。