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. 2020 Sep 14;20:880. doi: 10.1186/s12885-020-07368-1

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© The Author(s) 2020

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 3 — Mediation analysis illustrating the effect of tobacco smoking-altered methylation on gene expression in lung adenocarcinoma. a Scatter plots indicating the statistical significance of associations between methylations at three candidate CpG sites and tobacco smoking in lung adenocarcinoma. b Scatter plots indicating negative correlations between DNA methylation at three candidate CpG sites and gene expression in lung adenocarcinoma.c A diagram to illustrate a mediation analysis framework, where DNA methylation can be a mediator to affect the expression of tobacco smoking-altered genes. d Two candidate CpG sites are presented with significant mediation effects on gene expression, at P < 0.05. “ACME” refers to the average causal mediation effects via DNA methylation on gene expression