ABSTRACT

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.

摘要

DNA甲基化（DNAm）是研究最多的表观遗传修饰之一。DNAm 已成为测试环境暴露与流行病学研究结果之间关联的关键生物学机制和生物标志物。尽管以前的研究集中在 DNAm 与暴露/结果之间的关联，但测试 DNAm 对暴露与结果之间关联的中介作用是有用的。本范围审查的目的是介绍统计中介分析的方法论本质，并检查应用中介分析的新兴流行病学研究。我们使用截至 2020 年 12 月的在线数据库（PubMed、Scopus、Cochrane 和 CINAHL）对已发表的同行评审期刊进行了范围界定审查。我们通过初步筛选共提取了 219 篇文章。在对标题、摘要和全文进行审查后，共有 69 篇文章符合本次审查的条件。分配给每个类别的研究细分为：吸烟 13 项（18.8%），饮食摄入和饥荒 8 项（11.6%），其他生活方式因素 6 项（8.7%），临床终点 8 项（11.6%），环境 22 项化学暴露（31.9%），社会经济地位（SES）2（2.9%），遗传因素和种族（14.5%）10。在这篇综述中，我们为使用 DNAm 水平的中介分析提供了一个暴露范围的摘要。然而，我们在中介分析中发现了不同的方法和解释，这些方法和解释具有典型的问题，例如不同的细胞组成和组织特异性。进一步积累各种暴露的证据，