Department of Preventive Medical Sciences, Fujita Health University School of Medical Sciences, Toyoake, Japan.
Clinical Research Center, Nagasaki University Hospital, Nagasaki, Japan.
Epigenetics. 2022 Jun-Jul;17(7):759-785. doi: 10.1080/15592294.2021.1959736. Epub 2021 Aug 12.
DNA methylation (DNAm) is one of the most studied epigenetic modifications. DNAm has emerged as a key biological mechanism and biomarkers to test associations between environmental exposure and outcomes in epidemiological studies. Although previous studies have focused on associations between DNAm and either exposure/outcomes, it is useful to test for mediation of the association between exposure and outcome by DNAm. The purpose of this scoping review is to introduce the methodological essence of statistical mediation analysis and to examine emerging epidemiological research applying mediation analyses. We conducted this scoping review for published peer-reviewed journals on this topic using online databases (PubMed, Scopus, Cochrane, and CINAHL) ending in December 2020. We extracted a total of 219 articles by initial screening. After reviewing titles, abstracts, and full texts, a total of 69 articles were eligible for this review. The breakdown of studies assigned to each category was 13 for smoking (18.8%), 8 for dietary intake and famine (11.6%), 6 for other lifestyle factors (8.7%), 8 for clinical endpoints (11.6%), 22 for environmental chemical exposures (31.9%), 2 for socioeconomic status (SES) (2.9%), and 10 for genetic factors and race (14.5%). In this review, we provide an exposure-wide summary for the mediation analysis using DNAm levels. However, we found heterogenous methods and interpretations in mediation analysis with typical issues such as different cell compositions and tissue-specificity. Further accumulation of evidence with diverse exposures, populations and with rigorous methodology will be expected to provide further insight in the role of DNAm in disease susceptibility.
DNA 甲基化（DNAm）是研究最多的表观遗传修饰之一。在流行病学研究中，DNAm 已成为测试环境暴露与结果之间关联的关键生物学机制和生物标志物。尽管先前的研究集中在 DNAm 与暴露/结果之间的关联上，但测试 DNAm 是否可以介导暴露与结果之间的关联是很有用的。本范围综述的目的是介绍统计中介分析的方法本质，并检查新兴的应用中介分析的流行病学研究。我们使用在线数据库（PubMed、Scopus、Cochrane 和 CINAHL）对该主题的已发表同行评议期刊进行了这项范围综述，截止日期为 2020 年 12 月。通过初步筛选，我们共提取了 219 篇文章。在审查标题、摘要和全文后，共有 69 篇文章符合本综述的要求。分配给每个类别的研究数量分别为：吸烟 13 篇（18.8%）、饮食摄入和饥荒 8 篇（11.6%）、其他生活方式因素 6 篇（8.7%）、临床终点 8 篇（11.6%）、环境化学暴露 22 篇（31.9%）、社会经济地位（SES）2 篇（2.9%）、遗传因素和种族 10 篇（14.5%）。在本综述中，我们提供了使用 DNAm 水平进行中介分析的广泛暴露总结。然而，我们发现中介分析方法和解释存在异质性，存在典型问题，如不同的细胞成分和组织特异性。随着不同暴露、人群和严格方法学的证据的进一步积累，有望进一步了解 DNAm 在疾病易感性中的作用。
