Background

Metabolic diseases such as obesity are known to be driven by both environmental and genetic factors. Although genome-wide association studies of common variants and their impact on complex traits have provided some biological insight into disease etiology, identified genetic variants have been found to contribute only a small proportion to disease heritability, and to map mainly to non-coding regions of the genome. To link variants to function, association studies of cellular traits, such as epigenetic marks, in disease-relevant tissues are commonly applied.

Scope of the review

We review large-scale efforts to generate genome-wide maps of coordinated epigenetic marks and their utility in complex disease dissection with a focus on DNA methylation. We contrast DNA methylation profiling methods and discuss the advantages of using targeted methods for single-base resolution assessments of methylation levels across tissue-specific regulatory regions to deepen our understanding of contributing factors leading to complex diseases.

Major conclusions

Large-scale assessments of DNA methylation patterns in metabolic disease-linked study cohorts have provided insight into the impact of variable epigenetic variants in disease etiology. In-depth profiling of epigenetic marks at regulatory regions, particularly at tissue-specific elements, will be key to dissect the genetic and environmental components contributing to metabolic disease onset and progression.

中文翻译：

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捕获功能表观基因组以深入了解代谢疾病。

 背景

众所周知，肥胖等代谢疾病是由环境和遗传因素共同驱动的。尽管对常见变异及其对复杂性状的影响的全基因组关联研究为疾病病因学提供了一些生物学见解，但已发现已识别的遗传变异对疾病遗传性仅贡献一小部分，并且主要映射到疾病的非编码区域。基因组。为了将变异与功能联系起来，通常应用疾病相关组织中细胞特征（例如表观遗传标记）的关联研究。

 审查范围

我们回顾了生成协调表观遗传标记全基因组图谱的大规模努力及其在复杂疾病解剖中的效用，重点是 DNA 甲基化。我们对比了 DNA 甲基化分析方法，并讨论了使用靶向方法对跨组织特异性调控区域的甲基化水平进行单碱基分辨率评估的优势，以加深我们对导致复杂疾病的影响因素的理解。

 主要结论

对代谢疾病相关研究队列中 DNA 甲基化模式的大规模评估，深入了解了表观遗传变异对疾病病因学的影响。深入分析调控区域的表观遗传标记，特别是组织特异性元件，将是剖析导致代谢疾病发生和进展的遗传和环境成分的关键。